The role of the supplementary motor area in externally timed movement: the influence of predictability of movement timing

A significant role in the planning and preparation for voluntary movement has been ascribed to secondary motor areas located on the medial wall of the cerebral hemispheres, and in particular to the supplementary motor area (SMA). Within the SMA, rostral and caudal subdivisions have been described, and differential roles have been attributed to these regions in relation to movement planning, preparation and execution. We have used functional magnetic resonance imaging (fMRI) to investigate the role of the SMA in the timing of movement execution, by recording the fMRI signal from mesial pre-motor areas and primary sensorimotor cortex (SM1) during the execution of a simple motor task externally cued at predictable (regular) and unpredictable (irregular) time intervals. The mean rate of movement was matched in both experiments. There was a greater activation of caudal than rostral SMA with both predictably and unpredictably cued movements, and a doubling of the signal when the timing of the motor response was unpredictable. In contrast, there was no difference in the activation of primary sensorimotor cortex with the two tasks. The data demonstrate that the caudal SMA has an important role in the execution of externally cued movements. The results also suggest a greater role for this region in the performance of unpredictably timed compared with predictably timed movements, however a model is proposed (based on electrophysiological data) which shows how the difference in functional signal in these two situations can be explained on the basis of a difference in the time course of neuronal activation in the SMA, rather than in the overall degree of activation.     

Simple and complex movements in a patient with infarction of the right supplementary motor area

The role played by the supplementary motor area (SMA) in the higher-level organization of motor behaviour (motor programming) has been highlighted by the study of cerebral blood flow during voluntary movements in normal humans. We present a detailed physiological investigation from a patient with a right SMA lesion and show that the right SMA plays a role in programming simultaneous and sequential movements in both arms, though the contralateral arm was the more severely impaired. In addition, we obtained evidence to suggest that the precentral motor cortex may be more responsive to peripheral perturbations when the modulating influence of the SMA is absent. In view of the similarity of the physiological findings in this subject to those in patients with Parkinson's disease, we suggest that the defect of motor programming in Parkinson's disease is likely to reflect functional deafferentation of the SMA.     

Hemispherical asymmetry in human SMA during voluntary simple unilateral movements. An fMRI study

Functional magnetic resonance imaging (fMRI) was used to test the hypothesis of a prevailing role of left supplementary motor area (SMA) during voluntary right and left finger movements, in line with subjects' right hand preference. fMRI responses were quantified using task-related percent increase of the signal from statistically activated voxels in primary somatosensory (S1), primary motor (M1), and SMA cortical regions. Regional analysis comprised both extension and intensity of statistically activated groups of voxels. Results replicated previous fMRI evidence. Right M1 and S1 were much more activated during left rather than right movements, whereas such a difference was less evident in left M1 and S1. A novel finding consisted in an analogous functional hemispherical asymmetry in left and right SMA. Strikingly, left SMA activation did not differ statistically during right (contralateral) vs. left (ipsilateral) movements. It was concluded that, in right-handed subjects, left SMA plays a prevailing role in the control of voluntary movements.     

Laterality, somatotopy and reproducibility of the basal ganglia and motor cortex during motor tasks

We investigated the basal ganglia, motor cortex area 4, and supplementary motor area (SMA) using functional magnetic resonance imaging (fMRI) and five motor tasks: switching between finger and toe movements, writing, finger tapping, pronation/supination, and saccadic eye movements. We found reliable activation in the caudate nucleus and putamen in single subjects without the need for inter-subject averaging. Percent signal changes in basal ganglia were smaller by a factor of three than those in SMA or motor cortex (1% vs. 2.5-3%). There was a definite foot-dorsal, hand-ventral basal ganglia somatotopy, similar to prior data from primates. Saccadic eye movements activated the caudate nucleus significantly more than the other tasks did. Unilateral movements produced bilateral activation in the striatum even when motor cortex activation was unilateral. Surprisingly, bilateral performance of the tasks led, on average, to consistently smaller basal ganglia activation than did unilateral performance (P<0.001), suggesting less inhibition of contralateral movements during bilateral tasks. Moreover, there was a striking dominance pattern in basal ganglia motor activation: the left basal ganglia were more active than the right for right handers, regardless of the hand used. This lateralization appears much stronger than that previously reported for motor cortex. Comparisons of inter-subject and intra-subject reproducibility indicated a much larger variability in basal ganglia and SMA compared to motor cortex, in spite of similar percent signal changes in the latter two structures.     

Activation of supplementary motor areas during voluntary movements in man studied by measurement of focal cerebral blood flow (author's transl)]

Focal activation in the cerebral cortex during different motility and language tests in 52 patients examined by arteriography was studied by measuring focal cerebral blood flow (fCBF) by means of an apparatus of high resolution. A sterotactic or functional approach demonstrated that the upper premotor activation previously noted in certain types of movement, corresponds to supplementary motor area (SMA). A retrospective study of 157 maps of fCBF recorded during motor or verbal behaviour, compared to 90 recordings in subjects at rest, showed that SMA is involved in most voluntary movements, either verbal or non-verbal. An analysis of the results suggests that SMA acts during the establishment of new motor programs, and in the control of pre-established automatic activities, in response to internal and external stimuli.     

Movement-related potential measures of different modes of movement selection in Parkinson's disease

Movement-related potentials were recorded preceding self-paced voluntary movements in patients with Parkinson's disease and in healthy subjects of the same age group. We compared the Readiness Potential preceding joystick movements in a fixed direction and preceding joystick movements in freely selected directions. In normal subjects the Readiness Potential amplitude was higher preceding freely selected movements than preceding movements in a fixed direction. The Readiness Potential in Parkinson patients failed to be modified by the different modes of movement selection. The modulation of the Readiness Potential by different ways of preparing for movement might be due to the supplementary motor area (SMA) being more strongly engaged by tasks requiring internal control of movements than by tasks that are externally structured. The results suggest that this task-dependent variation of SMA activity is reduced in Parkinson's disease. A failing capacity to adapt SMA activity to different task demands has previously been suggested by evidence from positron emission tomography studies using similar tasks.     

The cortical effect of clapping in the human brain: A functional MRI study

Since development of functional MRI (fMRI), many studies have reported on cortical activation by external stimuli. However, there has been no fMRI study on the cortical effect of clapping. Using fMRI, we investigated the cortical activation effect of clapping in comparison with other motor tasks in the healthy human brain. Fourteen healthy volunteers were recruited. fMRI was performed using a 1.5-T Philips Gyroscan Intera with a standard head coil. Clapping, grasp-release movements, and sequential finger opposition of both hands were performed. Regions of interest (ROIs) were set at the primary sensori-motor cortex (SM1), supplementary motor cortex (SMA), and premotor cortex (PMC). The activated voxel number of all ROIs was in the following order: clapping, sequential opposition, and grasp-release movements. In the SM1, clapping showed the most significant activation, followed by sequential opposition, and grasp-release movements. By contrast, the PMC was most activated by sequential opposition, and then clapping and grasp-release movements, in order. As for the SMA, clapping evoked the most significant activation, followed by clapping, and grasp-release movements. We found that clapping showed the most significant cortical activation in ROIs among three motor tasks. Clapping appears to be an effective method for stimulation of the brain.     

The initiation of voluntary movements by the supplementary motor area

The hypothesis is formulated that in all voluntary movements the initial neuronal event is in the supplementary motor areas (SMA) of both cerebral hemispheres. Experimental support is provided by three lines of evidence. 1. In voluntary movements many neurones of the SMA are activated probably up to 200 ms before the pyramidal tract discharge. 2. Investigations of regional cerebral blood flow by the radioactive Xenon technique reveal that there is neuronal activity in the SMA of both sides during a continual series of voluntary movements, and that this even occurs when the movement is thought of, but not executed. 3. With voluntary movement there is initiation of a slow negative potential (the readiness potential, RP) at up to 0.8 s before the movement. The RP is maximum over the vertex, i.e. above the SMA, and is large there even in bilateral Parkinsonism when it is negligible over the motor cortex. An account is given of the SMA, particularly its connectivities to the basal ganglia and the cerebellum that are active in the preprogramming of a movement. The concept of motor programs is described and related to the action of the SMA. It is proposed that each mental intention acts on the SMA in a specific manner and that the SMA has an 'inventory' and the 'addresses' of stored subroutines of all learnt motor programs. Thus by its neuronal connectivities the SMA is able to bring about the desired movement. There is a discussion of the manner in which the mental act of intention calls forth neural actions in the SMA that eventually lead to the intended movement. Explanation is given on the basis of the dualist-interactionist hypothesis of mind-brain liaison. The challenge is to the physicalists to account for the observed phenomena in voluntary movement.     

Human supplementary motor area: a role in voluntary movements and its clinical significance]

There were two hypotheses of functions of supplementary motor area (SMA): supplementary vs. supramotor, in 1980s. Clinically, SMA can develop a very intractable seizure focus characterized by unique ictal motor symptoms, and its dysfunction is also strongly related to the cardinal clinical features in patients with Parkinson's disease and dystonia. In patients with intractable partial seizures arising from the mesial frontal area who needed clinically chronic implantation of the subdural electrode grids for 1-2 weeks prior to the focus resection, we recorded movement-related cortical potentials or Bereitschaftspotentials (BPs) prior to the voluntary movements. As the results, 1) SMA proper, a caudal part of SMA showed a somatotopy of BP generators in accordance with each part of the voluntary movements in the body, 2) bilateral SMAs were involved in each side of the body movements equally, and the amplitude did not differ from one in the contralateral primary motor area (MI), and thus it proved that SMA proper played as a significant role in preparation for voluntary movements as MI. Furthermore, we clarified the functional significance of pre-SMA with regard to sensorimotor integration, decision making, repetitive rate of voluntary movements, voluntary motor inhibition and negative motor response. Clinically we also clarified the pathophysiology of SMA seizures, and impairment of SMA function in Parkinson's disease and dystonia. We look forward to clinical application of brain potentials from SMA in the field of brain-computer interface such as assessment and restorative approach in patients with spinal cord injury, paraplegia or motor neuron disease.     

Human supplementary motor area: a role in voluntary movements and its clinical significance]

Clinically, seizures from supplementary motor area (SMA) are characterized by asymmetric bilateral tonic posturing without loss of awareness, and its dysfunction is also strongly related to the clinical cardinal features in patients with Parkinson's disease and dystonia. By investigating Bereitschaftspotentials (BPs) from SMA, the following normal functions are elucidated. 1) SMA proper, a caudal part of SMA showed a somatotopy of BP generators in accordance with each part of the voluntary movements in the body, 2) bilateral SMAs were involved in each side of the body movements equally, and the amplitude did not differ from one in the contralateral primary motor area (MI), 3) pre-SMA was strongly related sensorimotor integration, decision making, repetitive rate of voluntary movements, voluntary motor inhibition and negative motor response. We look forward to clinical application of brain potentials from SMA in the field of brain-computer interface such as assessment and restorative approach in patients with spinal cord injury, paraplegia or motor neuron disease.     

Readiness potentials preceding spontaneous motor acts: voluntary vs. involuntary control.

Libet et al. (1983) developed a method to compare the onset time of a readiness potential (RP) with the onset time of the corresponding intention to perform a spontaneous voluntary motor act. In relation to the onset of the RP, the time of conscious intention to move followed 350 msec later. From these results Libet (1985) concluded that the cerebral initiation of a spontaneous voluntary act begins unconsciously. We investigated the alternative interpretation that with the instruction to pay attention to feelings of 'wanting to move,' automatic and normally unconscious motor acts might have been brought to a level of conscious awareness. Therefore we conducted 3 kinds of experiment. In the first, RPs were measured from subjects performing unconscious movements. The second experiment was a replication of Libet's study while the third was a resting condition in which subjects looked for intentions to move introspectively. The results showed that RPs beginning approximately 500 msec before movement onset can be obtained with unconsciously as well as consciously performed spontaneous motor acts. The different scalp distributions of the two types of RP indicate that unconscious movements can be attributed to the activation of a contralateral process (lateral premotor system (LPS), primary motor cortex), whereas voluntary spontaneous motor acts seemed to be predominated by the medial premotor system (MPS). It is proposed that in the Libet situation focused attention on internal events led to the conscious detection of a normally unconscious process. This resulted in the activation of the MPS, especially the supplementary motor area (SMA), which released the starting signal for the execution of the motor act. We believe that the activation of the SMA and the urge to move occurred at the same time.     

Somesthetic function of supplementary motor area during voluntary movements.

To clarify the somesthetic functions of the supplementary motor area (SMA), we recorded the cortical potentials following the median nerve electric stimulation directly from the SMA and investigated the modulation caused by voluntary movements in two patients with intractable SMA seizures. The evoked potentials over the SMA consisted of positive (61.5ms) and negative (100.0 ms) peaks, which were enlarged by voluntary movements of the stimulated hand. The present finding is in strong contrast with the attenuation (gating) of the response at the primary sensorimotor area (SM1) and suggests that the voluntary movements differently modulate the somatosensory functions of SMA and SM1.     

Delayed experience of volition in Gilles de la Tourette syndrome

Gilles de la Tourette's syndrome (TS) is a neuropsychiatric movement disorder characterised by the presence of multiple tics. Tics have an unusual, intermediate status between voluntary and involuntary movements. This ambiguity might involve not just a disorder of movement generation but also an abnormality of voluntary experience. Here the experience of voluntary movements in adult patients with TS is investigated and compared with healthy controls. A group of adult TS patients and age matched control participants estimated the time of conscious intention to perform a simple keypress movement and movement onset. Patients with TS showed a delayed experience of intention relative to controls whereas estimates of the actual movement onset were similar for patients and controls. These data suggest an abnormal experience of volition in patients with TS. Delayed volition could either be an additional intrinsic feature of the syndrome or it could reflect a cognitive strategy to limit motor excitability, and thus tic generation, during voluntary action.     

Quantitative EEG analysis during motor function and music perception in Tourette's syndrome

Gilles de la Tourette's syndrome (TS) is a neurobehavioral disorder of childhood onset that is characterized by motor and vocal tics and associated behavioral disturbances including obsessive-compulsive symptoms. We performed 30 channel quantitative electroencephalograms (EEGs) on 13 Tourette patients and 26 controls and studied both resting and manumotor/music perception activation conditions. Resting EEGs did not show any differences between patients and controls, as known from the literature. However, during simple and complex hand movements, as well as music perception tasks, there were subtle differences predominantly in alpha frequency. They suggested reduced brain activation during motor tasks in frontal and central regions, and on music perception in temporal and parietal regions, respectively. These findings may add evidence to the functional neuroanatomy of Tourette syndrome, affecting more areas than disturbed motor circuits.     

Non-effective increase of fMRI-activation for motor performance in elder individuals

Motor performance declines with increasing age and it has been proposed that elder people might compensate for these deficits with increased cerebral activation. However, it is not known, whether increased activation - especially in motor areas of the contralateral and the ipsilateral cerebral hemisphere - might effectively contribute to motor performance or whether it is an ineffective way to counteract age related deficits in the motor system. We tested this question by mapping brain activation during performance of differentially demanding motor tasks in 18 young (mean 25.39 years) and 17 elderly (mean 66.65 years) healthy individuals. We tested a wide range of hand motor tasks from passive wrist movements, fist clenching at different frequencies, to a somatosensory-guided finger pinch task. In the elderly group functional activation was generally increased for all tasks with comparable motor performance for ipsilateral primary and secondary motor areas. The young group showed increased contralateral primary motor cortex activation for the more difficult somatosensory guided precision grip task. We correlated motor performance of the task with high difficulty and comparable performance with fMRI-activation. Elder participants showed a negative correlation for the ipsilateral supplementary motor area (SMA) and for the ipsilateral sensorimotor cortex (SM1). Young participants showed a positive correlation for contralateral SMA and SM1. Our data suggest an increased cerebral recruitment reflects an inefficient response to an age-related higher difficulty of task and is not an effective way to counteract age-related deficits in the motor system.     

Brain regions involved in voluntary movements as revealed by radioisotopic mapping of CBF or CMR-glucose changes

Mapping of cortical and subcortical grey matter active during voluntary movements by means of measurements of local increases of CBF or CMR-Glucose is reviewed. Most of the studies concern observations in man during hand movements using the intracarotid Xenon-133 injection technique, an approach that only allows to image the cortex of the hemisphere on one side (the injected side) of the brain. The results show that simple static or repetitive movements mainly activate the contralateral primary hand area (MI and SI); complex preprogrammed or spontaneous purposeful movements the supplementary motor area SMA on both sides increase in CBF/CMR-glucose and even internally ("mentally") going through the trained movements, causes such changes; complex purposeful movements also activate the premotor cortex, a response that is bilateral with greatest response contralaterally. Studies in patients with movement disorders are scant, but with the ongoing improvements in technique activation studies in selected patients may become an important tool in clinical neurophysiology/neuropsychology.     

The initiation of voluntary movements by the supplementary motor area

Summary The hypothesis is formulated that in all voluntary movements the initial neuronal event is in the supplementary motor areas (SMA) of both cerebral hemispheres.Experimental support is provided by three lines of evidence. 1. In voluntary movements many neurones of the SMA are activated probably up to 200 ms before the pyramidal tract discharge. 2. Investigations of regional cerebral blood flow by the radioactive Xenon technique reveal that there is neuronal activity in the SMA of both sides during a continual series of voluntary movements, and that this even occurs when the movement is thought of, but not excuted. 3. With voluntary movement there is initiation of a slow negative potential (the readiness potential, RP) at up to 0.8 s before the movement. The RP is maximum over the vertex, i.e. above the SMA, and is large there even in bilateral Parkinsonism when it is negligible over the motor cortex.An account is given of the SMA, particularly its connectivities to the basal ganglia and the cerebellum that are active in the preprogramming of a movement. The concept of motor programs is described and related to the action of the SMA. It is proposed that each mental intention acts on the SMA in a specific manner and that the SMA has an inventory and the addresses of stored subroutines of all learnt motor programs. Thus by its neuronal connectivities the SMA is able to bring about the desired movement.There is a discussion of the manner in which the mental act of intention calls forth neural actions in the SMA that eventually lead to the intended movement. Explanation is given on the basis of the dualist-interactionist hypothesis of mind-brain liaison. The challenge is to the physicalists to account for the observed phenomena in voluntary movement.Dedicated to Prof. Richard Jung on the occasion of his 70th birthday     

Relation of bimanual coordination to activation in the sensorimotor cortex and supplementary motor area: analysis using functional magnetic resonance imaging

The aim of this study was to analyze how functional activation in the supplementary motor area (SMA) and sensorimotor cortex (SMC) is related to bimanual coordination using functional magnetic resonance imaging. Subjects included 24 healthy volunteers, 15 of whom were right-handed and 9 left-handed. Three kinds of activation tasks, all of which required the repetitive closing and opening of a fist, were performed: unimanual movement of the nonpreferred hand (task A); simultaneous, agonistic movement of both hands (task B); simultaneous, antagonistic movement of both hands (task C). The SMA activation during task C was more pronounced than that during the other two tasks for right and left handers. The results suggested that the activation of the SMA, at least during a simple motion used in the present study, was little influenced by whether the motion was unimanual or bimanual but instead how the bimanual motion was composed of the motion element of a single hand. The SMC activation during task C was significantly larger than that during task B, whereas hemispheric differences in the activation were not found. This indicated that the complexity of the bimanual movement also affected the SMC activation.     

Nigrostriatal dopamine system and motor lateralization

The mechanism by which most people favor use of the right hand remains unknown. It has been proposed that asymmetries in the nigrostriatal dopamine system may be related to motor lateralization in humans. We explored this hypothesis in vivo by using [18F]fluorodopa positron emission tomography. Whereas the degree of right hand preference was found to correlate with left putamen dominance as assessed by asymmetry in fluorodopa uptake (K(i)), right caudate dominance was positively correlated with the level of performance during simultaneous bimanual movements in right-handed normal subjects. In addition, right-handed patients with Parkinson's disease with higher right than left caudate K(i) performed much better in bimanual movement tests than those in whom the K(i) value of the left caudate was higher than that of the right. These findings support the notion that the nigrostriatal dopaminergic system may play a role in motor lateralization, and suggest a functional model for bimanual movements. We propose that the skill for performing simultaneous bilateral hand movements in right-handed subjects might depend upon both the activation (through the dominant left putamen circuitry) of the left supplementary motor area (SMA), and the inhibition (through the right caudate circuitry) of motor programs stored in the right SMA.     

Oculomotor abnormalities in boys with tourette syndrome with and without ADHD.

OBJECTIVE: To assess saccadic eye movements in boys with Tourette syndrome (TS) with and without attention-deficit hyperactivity disorder (ADHD), comparing performance with that of an age-matched group of male controls. METHOD: Three different saccade tasks (prosaccades, antisaccades, and memory-guided saccades) were used to examine functions necessary for the planning and execution of eye movements, including motor response preparation, response inhibition, and working memory. The study included 14 boys with TS without ADHD (TS-only), 11 boys with TS and ADHD (TS+ADHD), and 10 male controls. RESULTS: Latency of prosaccades was prolonged in boys with TS (both with and without ADHD) compared with controls. Variability in prosaccade latency was greater in the groups of boys with TS+ADHD compared with both the TS-only and control groups. Response inhibition errors on both the antisaccade task (directional errors) and memory-guided saccade task (anticipatory errors) were increased in boys with TS+ADHD compared with those with TS-only. There were no significant differences among the three groups in accuracy of memory-guided saccades. CONCLUSIONS: Oculomotor findings suggest that TS is associated with delay in initiation of motor response as evidenced by excessive latency on prosaccades. Signs of impaired response inhibition and variability in motor response appear to be associated with the presence of ADHD.