Biomedical subjects

R E Passingham

Publications and source records attributed to R E Passingham.

At least 37 records · Page 2Linked to original sources

PubMed2001

The attentional role of the left parietal cortex: the distinct lateralization and localization of motor attention in the human brain.

It is widely agreed that visuospatial orienting attention depends on a network of frontal and parietal areas in the right hemisphere. It is thought that the visuospatial orienting role of the right parietal lobe is related to its role in the production of overt eye movements. The experiments reported here test the possibility that other parietal regions may be important for directing attention in relation to response modalities other than eye movement. Specifically, we used positron emission tomography (PET) to test the hypothesis that a 'left' parietal area, the supramarginal gyrus, is important for attention in relation to limb movements (Rushworth et al., 1997; Rushworth, Ellison, & Walsh, in press). We have referred to this process as 'motor attention' to distinguish it from orienting attention. In one condition subjects spent most of the scanning period covertly attending to 'left' hand movements that they were about to make. Activity in this first condition was compared with a second condition with identical stimuli and movement responses but lacking motor attention periods. Comparison of the conditions revealed that motor attention-related activity was almost exclusively restricted to the 'left' hemisphere despite the fact that subjects only ever made ipsilateral, left-hand responses. Left parietal activity was prominent in this comparison, within the parietal lobe the critical region for motor attention was the supramarginal gyrus and the adjacent anterior intraparietal sulcus (AIP), a region anterior to the posterior parietal cortex identified with orienting attention. In a second part of the experiment we compared a condition in which subjects covertly rehearsed verbal responses with a condition in which they made verbal responses immediately without rehearsal. A comparison of the two conditions revealed verbal rehearsal-related activity in several anterior left hemisphere areas including Broca's area. The lack of verbal rehearsal-related activity in the left supra-marginal gyrus confirms that this area plays a direct role in motor attention that cannot be attributed to any strategy of verbal mediation. The results also provide evidence concerning the importance of ventral premotor (PMv) and Broca's area in motor attention and language processes.

Adult↗

PubMed2001

Working memory for location and time: activity in prefrontal area 46 relates to selection rather than maintenance in memory.

The role of the dorsal prefrontal cortex in working memory remains controversial. Influential proposals include a role in the maintenance of domain-specific information, and the processes of executive functions on remembered information. We used event-related functional magnetic resonance imaging to demonstrate a functional dissociation within prefrontal cortex in terms of the components of complex working memory tasks. The maintenance in working memory of spatial locations and their temporal order was associated with activation of area 8 and intraparietal cortex. In contrast, the selection of one location, according to its order, was associated with a distinct frontoparietal network, including dorsolateral prefrontal area 46, ventrolateral prefrontal cortex and anterior cingulate cortex and medial parietal cortex. The different contributions of these areas to selection are considered in the light of recent electrophysiological and lesion studies. We suggest a general role of the dorsolateral prefrontal area 46 in attentional selection, including selection from within working memory.

Adult↗

PubMed2001

Contrasting the dorsal and ventral visual systems: guidance of movement versus decision making.

It is widely accepted that the ventral visual pathways are involved in the identification of objects and the dorsal visual pathways in the visual guidance of reaching and grasping movements. But there are also situations, such as in a choice reaction time task, in which the subjects must select between actions on the basis of visual cues. This paper uses brain imaging to explore the pathways that are involved. Studies using PET and fMRI show that when subjects learn which actions are appropriate given the visual context, there are learning-related increases in the inferotemporal cortex and the ventral prefrontal cortex to which it projects. An event-related fMRI study shows that the activity in the inferotemporal cortex is time-locked to the presentation of the visual cue and the activity in the ventral prefrontal cortex to the response. Finally two PET studies directly compare the dorsal and ventral systems. In the second of these the subjects either move their finger on a moving target or identify the direction of movement and press one of two buttons to report the direction. When the subjects report the direction there is activity in the middle temporal gyrus and ventral prefrontal cortex. It is suggested that, when subjects must consciously identify the context and decide on the appropriate action, ventral pathways are involved.

Association Learning↗

PubMed2001

The cerebellum and parietal cortex play a specific role in coordination: a PET study.

The synthesis of complex, coordinated movements from simple actions is an important aspect of motor control. Lesion studies have revealed specific brain areas, particularly the cerebellum, to be essential for a variety of coordinated movements, and lend support to the view that the cerebellum is engaged in the integration of simple movements into compound ones. A PET study was therefore conducted to show which brain areas were active specifically during the coordinated execution of an arm and finger movement to visual targets. A two-by-two factorial design was employed, in which subjects either made arm or finger movements alone, made coordinated arm-finger movements, or made no movements. Voxels were identified where activity was significantly greater during the execution of coordinated movements than when movements were made alone and in which this increased activity could not be accounted for simply by the additive effects of the activations for each movement in isolation. The behavioral results showed that subjects coordinated arm and finger movements well during coordination scans. Coordination-specific activations were found in left anterior lobe and bilaterally in the paramedian lobules of the cerebellum. These are known to receive forelimb-specific spinocerebellar proprioceptive inputs that may be related to multijoint movements. The same areas also receive corticocerebellar afference from motor areas that may convey efference copy information to the cerebellum. Coordination-specific activations were also seen in areas of the posterior parietal cortex. The results provide direct evidence in healthy human subjects of specific cerebellar engagement during the coordination of movement, over and above the control of constituent movements.

Adult↗

PubMed2001

Learning arbitrary visuomotor associations: temporal dynamic of brain activity.

Primates can give behavioral responses on the basis of arbitrary, context-dependent rules. When sensory instructions and behavioral responses are associated by arbitrary rules, these rules need to be learned. This study investigates the temporal dynamics of functional segregation at the basis of visuomotor associative learning in humans, isolating specific learning-related changes in neurovascular activity across the whole brain. We have used fMRI to measure human brain activity during performance of two tasks requiring the association of visual patterns with motor responses. Both tasks were learned by trial and error, either before (visuomotor control) or during (visuomotor learning) the scanning session. Epochs of tasks performance ( approximately 30 s) were alternated with a baseline period over the whole scanning session ( approximately 50 min). We have assessed both linear and nonlinear modulations in the differential signal between tasks, independently from overall task differences. The performance indices of the visuomotor learning task smoothly converged onto the values of a steady-state control condition, according to nonlinear timecourses. Specific visuomotor learning-related activity has been found over a distributed cortical network, centred on a temporo-prefrontal circuit. These cortical time-modulated activities were supported early in learning by the hippocampal/parahippocampal complex, and late in learning by the basal ganglia system. These findings suggest the inferior temporal and the ventral prefrontal cortex are critical neural nodes for integrating perceptual information with executive processes.

Adult↗

PubMed2001

Predicting sensory events. The role of the cerebellum in motor learning.

There is growing evidence that the cerebellum is involved in the implicit learning of movement sequences. On the serial reaction time (RT) task patients with cerebellar lesions fail to demonstrate normal decreases in RT and we have shown a similar effect in monkeys with bilateral cerebellar lesions. However, it is not clear if this impairment is unique to sequence learning or whether the cerebellum is also involved in the learning of discrete responses to predictable visual targets. We investigated this possibility in another group of monkeys with bilateral lesions of the cerebellum centred on the lateral nuclei. Three animals were pre-operatively trained to make rapid manual responses to a single target appearing on a touch-sensitive VDU screen. In one condition, a target could appear at any of three possible locations (spatially unpredictable). In a second condition the target always appeared in the same place (spatially predictable). A third condition was similar to the second except that the onset of the target was temporally predictable whereas in the previous conditions this parameter was randomized. Following the lesions, the RT savings earned on the conditions in which the cues were predictable were abolished. This was despite a lack of significant increase in movement times. The results imply that the animals were either failing to predict the spatial location or time of presentation of the target, or that they were unable to use their prediction to improve their reaction times. The function of the cerebellum in motor sequence learning may therefore be part of a more general operation in learning to prepare responses to predictable sensory events.

Animals↗

PubMed2001

Neural correlates of visuomotor associations. Spatial rules compared with arbitrary rules.

A green button may be the target of a movement, or it may instruct the opening of an adjacent door. In the first case, its spatial configuration serves to guide the hand, whereas in the second case its colour allows a decision between alternative courses of action. This study contrasts these two categories of visuomotor transformation. Our goal was to test the hypothesis that visual information can influence the motor system through different, task-dependent pathways. We used positron emission tomography (PET) to measure human brain activity during the performance of two tasks requiring the transformation of visual stimuli to motor responses. The stimuli instructed either a spatially congruent grasping movement or an arbitrarily associated hand movement. The experimental design emphasised preparatory- over movement-related activity. We expected ventral parieto-precentral regions to contribute to the visuomotor transformations underlying grasping movements, and fronto-striatal circuitry to contribute to the selection of actions on the basis of associative rules. We found that selecting between alternative courses of action on the basis of associative rules specifically involved ventral prefrontal, striatal and dorsal precentral areas. Conversely, spatially congruent grasping movements evoked specific differential responses in ventral precentral and parietal regions. The results suggest that visual information can flow through the dorsal system to determine how actions are performed, but that fronto-striatal loops are involved in specifying which action should be performed in the current context.

Adult↗

PubMed2001

Cerebral dominance for action in the human brain: the selection of actions.

PET was used to study cerebral dominance for the selection of action. In one condition the subjects moved one of two fingers depending on the cue presented (choice reaction time), and in another they moved the same finger whatever the cue (simple reaction time). There was also a baseline condition in which cues were shown but no movements were made. A conjunction analysis was performed to reveal those areas which were more activated for the choice versus simple reaction time, irrespective of whether the right or left hand was used. The activations were in prefrontal, premotor and intraparietal areas, and they were all in the left hemisphere. Thus, while there were activations in the right hemisphere for the choice versus simple reaction time task when the subjects used their left (contralateral) hand, there were activations in left prefrontal, premotor and parietal areas whether the right (contralateral) or left (ipsilateral) hands were used. It is argued that the results suggest that the left hemisphere is dominant not only for speech but also for action in general.

Adult↗

PubMed2001

Imaging the mental components of a planning task.

The Tower of London task (TOL) has been widely used to assess the ability to plan. We used H(2)O(15)-positron emission tomography to isolate some of the cognitive components of the task. Ten male volunteers were scanned twice in each of six conditions. In two conditions (plan) the subjects had to plan the best solution to TOL problems. In two other conditions (plan-control) the subjects were required to generate four moves without being constrained by a goal. In plan and plan-control tasks the subjects either planned the moves and then executed them (MOVE conditions) or imagined the necessary moves (IMAGINE conditions). The plan and plan-control tasks were matched for the working memory load and "initial thinking time". A visuomotor control task and rest served as baseline conditions. Performance on the plan tasks, in contrast to the baseline conditions, was associated with activation in the dorsal prefrontal cortex, premotor and parietal cortex, and cerebellum. Performance of the plan-control tasks was associated with activation of the same areas. Contrasting the plan with the plan-control tasks revealed no residual activation in the prefrontal cortex. These data show that the activity of the dorsolateral prefrontal cortex on the TOL can be accounted for by the components of generating, selecting and/or remembering mental moves. The task of relating the moves to the goal involves a comparison with a representation of the goal in posterior association areas. We did not find evidence that activation of the dorsal prefrontal cortex is specifically related to the evaluation of a path towards a specified goal, a key component of planning.

Adult↗

PubMed2000

Oral dyspraxia in inherited speech and language impairment and acquired dysphasia.

Half of the members of the KE family suffer from an inherited verbal dyspraxia. The affected members of the family have a lasting impairment in phonology and syntax. They were given various tests of oral praxis to investigate whether their deficit extends to nonverbal movements. Performance was compared to adult patients with acquired nonfluent dysphasia, those with comparable right-hemisphere lesions, and age-matched controls. Affected family members and patients with nonfluent dysphasia were impaired overall at performing oral movements, particularly combinations of movements. It is concluded that affected members of the KE family resemble patients with acquired dysphasia in having difficulties with oral praxis and that speech and language problems of affected family members arise from a lower level disorder.

Adolescent↗

PubMed2000

Pitch and timing abilities in inherited speech and language impairment.

Members of the KE family who suffer from an inherited developmental speech-and-language disorder and normal, age-matched, controls were tested on musical abilities, including perception and production of pitch and rhythm. Affected family members were not deficient in either the perception or production of pitch, whether this involved either single notes or familiar melodies. However, they were deficient in both the perception and production of rhythm in both vocal and manual modalities. It is concluded that intonation abilities are not impaired in the affected family members, whereas their timing abilities are impaired. Neither their linguistic nor oral praxic deficits can be at the root of their impairment in timing; rather, the reverse may be true.

Adolescent↗

PubMed2000

Pitch and timing abilities in adult left-hemisphere-dysphasic and right-hemisphere-damaged subjects.

The production and perception of pitch and rhythm were tested in patients with acquired unilateral left-hemisphere (LH) lesions (and subsequent motor dysphasia, n = 13), patients with unilateral right-hemisphere (RH) lesions (n = 14), and normal age-matched controls. While the LH dysphasic subjects were not generally impaired on the production or perception of pitch, they were grossly impaired on the production and perception of rhythm. The RH subjects, in contrast, were impaired on measures of pitch perception and production, including the discrimination and production of single notes and of melodies. It is concluded that the two hemispheres differ in their specialization for the perception and production of pitch and rhythm.

Adult↗

PubMed2000

The prefrontal cortex: response selection or maintenance within working memory?

It is controversial whether the dorsolateral prefrontal cortex is involved in the maintenance of items in working memory or in the selection of responses. We used event-related functional magnetic resonance imaging to study the performance of a spatial working memory task by humans. We distinguished the maintenance of spatial items from the selection of an item from memory to guide a response. Selection, but not maintenance, was associated with activation of prefrontal area 46 of the dorsal lateral prefrontal cortex. In contrast, maintenance was associated with activation of prefrontal area 8 and the intraparietal cortex. The results support a role for the dorsal prefrontal cortex in the selection of representations. This accounts for the fact that this area is activated both when subjects select between items on working memory tasks and when they freely select between movements on tasks of willed action.

Animals↗

PubMed2000

Specialisation within the prefrontal cortex: the ventral prefrontal cortex and associative learning.

This paper provides evidence that the ventral prefrontal cortex plays a role in the learning of tasks in which subjects must learn to associate visual cues and responses. Imaging with both positron-emission tomography (PET) and functional magnetic-resonance imaging (fMRI) reveals learning-related increases in activity when normal subjects learn visual associative tasks. Evidence is also presented from an event-related fMRI study that activity in this area is time-locked both to the presentation of the visual stimuli and also to the time of the motor response. Finally, it is shown in a study of monkeys that removal of the ventral prefrontal area 12 (including 45 A) impairs the ability of monkeys to relearn a visual associative task (visual matching), even though there were no demands on working memory. It is, therefore, proposed that the ventral prefrontal cortex constitutes part of the circuitry via which associations are formed between visual cues and the actions or choices that they specify. On the basis of the existing anatomical and electrophysiological data, it is argued that the prefrontal cortex is the only area that can represent cues, responses and outcomes.

Animals↗

PubMed2000

The cerebellum and cognition: cerebellar lesions impair sequence learning but not conditional visuomotor learning in monkeys.

Claims that the cerebellum contributes to cognitive processing in humans have arisen from both functional neuroimaging and patient studies. These claims challenge traditional theories of cerebellar function that ascribe motor functions to this structure. We trained monkeys to perform both a visuomotor conditional associative learning task and a visually guided sequence task, and studied the effects of bilateral excitotoxic lesions in the lateral cerebellar nuclei. In the first experiment three operated monkeys showed a small impairment in post-operative retention of a visuomotor associative task (A) but were then not impaired in learning a new task (B). However, the impairment on A could have been due to a problem in making the movements themselves. In a second experiment we therefore gave the three control animals a further pre-operative retest on both A and B and then tested after surgery on retention of both tasks. Though again the animals showed motor problems on task A, they reached criterion, and at this stage could clearly make both movements satisfactorily. The critical test was then retention of task B, and they were not impaired. In the final experiment (serial reaction time task) the monkeys response times on a repeating visuomotor sequence were compared with those for a pseudo-random control sequence. After bilateral nuclei lesions they were slow to execute the pre-operatively learned sequence but were still faster on this than on the control task. However, when they were then given a new repeating sequence to learn, they never performed the sequence as quickly as they had on retention of the first sequence. We conclude that the cerebellum is not essential for the learning or recall of stimulus-response associations but that it is crucially involved in the process by which motor sequences become automatic with extended practice.

Animals↗

PubMed2000

Self-initiated versus externally triggered movements. II. The effect of movement predictability on regional cerebral blood flow.

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.

Adult↗

PubMed2000

Temporary inactivation in the primate motor thalamus during visually triggered and internally generated limb movements.

To better understand the contribution of cerebellar- and basal ganglia-receiving areas of the thalamus [ventral posterolateral nucleus, pars oralis (VPLo), area X, ventral lateral nucleus, pars oralis (VLo), or ventral anterior nucleus, pars parvicellularis (VApc)] to movements based on external versus internal cues, we temporarily inactivated these individual nuclei in two monkeys trained to make visually triggered (VT) and internally generated (IG) limb movements. Infusions of lignocaine centered within VPLo caused hemiplegia during which movements of the contralateral arm rarely were performed in either task for a short period of time ( approximately 5-30 min). When VT responses were produced, they had prolonged reaction times and movement times and a higher incidence of trajectory abnormalities compared with responses produced during the preinfusion baseline period. In contrast, those IG responses that were produced remained relatively normal. Infusions centered within area X never caused hemiplegia. The only deficits observed were an increase in reaction time and movement amplitude variability and a higher incidence of trajectory abnormalities during VT trials. Every other aspect of both the VT and IG movements remained unchanged. Infusions centered within VLo reduced the number of movements attempted during each block of trials. This did not appear to be due to hemiplegia, however, as voluntary movements easily could be elicited outside of the trained tasks. The other main deficit resulting from inactivation of VLo was an increased reaction time in the VT task. Finally, infusions centered within VApc caused IG movements to become slower and smaller in amplitude, whereas VT movements remained unchanged. Control infusions with saline did not cause any consistent deficits. This pattern of results implies that VPLo and VLo play a role in the production of movements in general regardless of the context under which they are performed. They also suggest that VPLo contributes more specifically to the execution of movements that are visually triggered and guided, whereas area X contributes specifically to the initiation of such movements. In contrast, VApc appears to play a role in the execution of movements based on internal cues. These results are consistent with the hypothesis that specific subcircuits within the cerebello- and basal ganglio-thalamo-cortical systems preferentially contribute to movements based on external versus internal cues.

Analysis of Variance↗

PubMed2000

Learning- and expectation-related changes in the human brain during motor learning.

We have studied a simple form of motor learning in the human brain so as to isolate activity related to motor learning and the prediction of sensory events. Whole-brain, event-related functional magnetic resonance imaging (fMRI) was used to record activity during classical discriminative delay eyeblink conditioning. Auditory conditioned stimulus (CS+) trials were presented either with a corneal airpuff unconditioned stimulus (US, paired), or without a US (unpaired). Auditory CS- trials were never reinforced with a US. Trials were presented pseudorandomly, 66 times each. The subjects gradually produced conditioned responses to CS+ trials, while increasingly differentiating between CS+ and CS- trials. The increasing difference between hemodynamic responses for unpaired CS+ and for CS- trials evolved slowly during conditioning in the ipsilateral cerebellar cortex (Crus I/Lobule HVI), contralateral motor cortex and hippocampus. To localize changes that were related to sensory prediction, we compared trials on which the expected airpuff US failed to occur (Unpaired CS+) with trials on which it occurred as expected (Paired CS+). Error-related signals in the contralateral cerebellum and somatosensory cortex were seen to increase during learning as the sensory prediction became stronger. The changes seen in the ipsilateral cerebellar cortex may be due either to the violations of sensory predictions, or to learning-related increases in the excitability of cerebellar neurons to presentations of the CS+.

Acoustic Stimulation↗