Philip D. Nixon

CORTICAL AREAS AND THE SELECTION OF MOVEMENT : A STUDY WITH POSITRON EMISSION TOMOGRAPHY

SummaryRegional 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.

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.

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

Abstract 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.

The Inferior Frontal Gyrus and Phonological Processing: An Investigation using rTMS

Repetitive transcranial magnetic stimulation (rTMS) offers a powerful new technique for investigating the distinct contributions of the cortical language areas. We have used this method to examine the role of the left inferior frontal gyrus (IFG) in phonological processing and verbal working memory. Functional neuroimaging studies have implicated the posterior part of the left IFG in both phonological decision making and subvocal rehearsal mechanisms, but imaging is a correlational method and it is therefore necessary to determine whether this region is essential for such processes. In this paper we present the results of two experiments in which rTMS was applied over the frontal operculum while subjects performed a delayed phonological matching task. We compared the effects of disrupting this area either during the delay (memory) phase or at the response (decision) phase of the task. Delivered at a time when subjects were required to remember the sound of a visually presented word, rTMS impaired the accuracy with which they subsequently performed the task. However, when delivered later in the trial, as the subjects compared the remembered word with a given pseudoword, rTMS did not impair accuracy. Performance by the same subjects on a control task that required the processing of nonverbal visual stimuli was unaffected by the rTMS. Similarly, performance on both tasks was unaffected by rTMS delivered over a more anterior site (pars triangularis). We conclude that the opercular region of the IFG is necessary for the normal operation of phonologically based working memory mechanisms. Furthermore, this study shows that rTMS can shed further light on the precise role of cortical language areas in humans.

The functions of the medial premotor cortex

We report several studies on the effects of removing the medial premotor cortex (supplementary motor area) in monkeys. The removal of this area alone does not cause either paralysis or akinesia. However, the animals were poor at performing a simple learned task in which they had to carry out an arbitrary action: they were taught to raise their arm in order to obtain food in a foodwell below. They were impaired whether they worked in the light or the dark. They were impaired when they had to perform the movements at their own pace, but much less impaired when a tone paced performance.Monkeys with lesions in the anterior cingulate cortex were as impaired as monkeys with medial premotor lesions at performing this task at their own pace. However, monkeys with lateral premotor lesions were less impaired. We conclude that the medial premotor areas play a crucial role in the performance of learned movements when there is no external stimulus to prompt performance.

The left hemisphere and the selection of learned actions.

The left hemispheres dominance for movement is well known. The basis of its dominance is less clear. We have tested 16 left hemisphere (LH) patients, 17 right hemisphere (RH) patients and 12 neurologically normal controls on a battery of five tasks. The tasks were based on animal lesion and recording studies, and human imaging and magnetic stimulation studies that identified two distributed systems that are important for the selection of motor responses and object-oriented responses. The LH patients were impaired on three response selection tasks: learning to select between joystick movement responses instructed by visual cues; learning to select between analogous object-oriented responses instructed by visual cues; learning to select movements in a sequence. Although we replicated the finding that LH damage impairs sequencing, some of the impaired tasks had no sequencing element. We therefore argue that the LH deficits are best explained as an impairment of response selection. This was confirmed by showing that LH subjects were unimpaired on a more demanding task-object discrimination learning-which imposed a greater memory load but had no response selection element. Moreover, the LH deficits could not be attributed to disorganization of movement kinematics. The lesions of the impaired LH group were widespread but always included the distributed systems known to be important for response selection-the dorsolateral frontal and parietal cortices, striatum, thalamus and white matter fascicles.

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.

The role of the cerebellum in preparing responses to predictable sensory events.

Despite numerous studies on the effects of lesions of the mammalian cerebellum on coordination, adaptation and learning, the precise nature of this structure’s contribution to motor control remains controversial. This paper reviews the results of a series of behavioural studies with monkeys trained to make rapid, accurate sequences of responses to visual targets. The effects of discrete cerebellar lesions on the performance of these animals is discussed in the light of recent theories about how the cerebellum might be concerned with learning to anticipate certain kinds of sensory events. Additional studies are considered that advocate sensory prediction as a fundamental cerebellar function that could contribute to many of the behavioural processes with which the cerebellum has been implicated. In particular, it is demonstrated how such information could be employed in the augmentation of motor learning by the formation of expectations about the sensory feedback arising from movements and interactions with the environment. Whilst it is argued that the cerebellum may not be unique in being able to perform such functions, comparative anatomical studies suggest that it may operate with an unequalled degree of temporal precision. Such precision forms the signature of skilled motor acts.

Parietal cortex and movement II. Spatial representation

Abstract 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.

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

Abstract. 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.