Brain, Vol. 122, No. 7, 1357-1366,
July 1999
© 1999 Oxford University Press
Abnormal cortical processing of voluntary muscle relaxation in patients with focal hand dystonia studied by movement-related potentials
1 Departments of Brain Pathophysiology 2 Neurology, Kyoto University School of Medicine and 3 Department of Neurology, Miyazaki Prefectural Hospital of Nobeoka, Japan.
Correspondence to:
Dr Hiroshi Shibasaki, Department of Brain Pathophysiology, Kyoto University School of Medicine, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan E-mail: shib{at}kuhp.kyoto-u.ac.jp
 |
Abstract |
|---|
 Top Abstract IntroductionMaterial and methodsResultsDiscussionReferences |
|---|
In order to clarify the abnormality in cortical motor preparation for voluntary muscle relaxation of the hand in patients with focal hand dystonia, Bereitschaftspotentials (BPs) preceding voluntary muscle contraction and relaxation were recorded in eight patients (three with simple writer's cramp and five with dystonic writer's cramp), and were compared with those from 10 normal subjects. Voluntary muscle relaxation: after keeping the right wrist in an extended position for > 5 s, the subject let the hand drop by voluntarily terminating muscle contraction of the wrist extensor without any associated muscle contraction. Voluntary muscle contraction: the right wrist was flexed by voluntarily contracting the wrist flexor muscle. Scalp EEGs were recorded from 11 electrodes placed over the frontal, central and parietal areas. In the control group, the BP measured at the movement onset was maximal at the left central area (C1), and distributed predominantly over the left hemisphere equally in both the contraction and relaxation tasks. In the focal hand dystonia group, BP was maximal at C1 in the contraction task, whereas, in the relaxation task, it was maximal at the midline central area (Cz) and symmetrically distributed. At the left central area, the BP amplitude in the focal hand dystonia group was diminished significantly in the relaxation task compared with the contraction task (P < 0.05). The present results demonstrate for the first time that the cortical preparatory process for voluntary muscle relaxation, or motor inhibition, is abnormal in focal hand dystonia.
focal hand dystonia; central motor control; voluntary muscle relaxation; movement-related cortical potential
ANOVA = analysis of variance; BP = Bereitschaftspotential; MP = motor potential; MRCP = movement-related cortical potential; SI–MI = primary sensorimotor cortex; SMA = supplementary motor area; TMS = transcranial magnetic stimulation
|
Introduction |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
Dystonia is defined as a syndrome of sustained muscle contraction, frequently causing twisting and repetitive movements, or abnormal postures (Fahn, 1988
). Dystonic movements typically are aggravated by an attempt to perform an action (Oppenheim, 1911). Recently, physiological studies suggested an abnormality in the cortical motor control system in patients with dystonia. PET studies in patients with dystonia of various forms showed hypometabolism of glucose in the basal ganglia, thalamus and prefrontal association cortices (Karbe et al., 1992), and diminished blood flow changes in the sensorimotor and supplementary motor areas in response to various activation tasks (Tempel and Perlmutter, 1990, 1993; Ceballos-Baumann et al., 1995, 1997). An abnormal cortical sensorimotor integration mechanism was also shown by using electrophysiological methods (Kaji et al., 1995a; Ikeda et al., 1996) and a biokinetic approach (Odegren et al., 1996).
Movement-related cortical potential (MRCP) preceding self-paced, repetitive voluntary muscle contraction consists of at least two slow negative shifts (Kornhuber and Deecke, 1965; Shibasaki et al., 1980). The early part [Bereitschaftspotential (BP) or NS1] is maximal at the central vertex and symmetrically distributed over the scalp, whereas the later part (NS' or NS2) is larger at the central area contralateral to the movement (Shibasaki et al., 1980). These potentials are known to reflect a central motor control process in humans, and a number of studies employed this technique to investigate the mechanism of movement disorders (Deecke et al., 1977; Shibasaki et al., 1978; Barrett et al., 1986; Dick et al., 1989). Abnormalities of MRCP were reported in patients with various types of dystonia. Fève et al. showed diminished MRCP amplitude during wrist flexion in 15 patients with dystonia due to lesions in the basal ganglia and thalamus (Fève et al., 1994). In patients with idiopathic torsion dystonia, in addition to the diminished amplitude of NS' at the midline leads compared with normal controls, its horizontal distribution for the finger extension task was not lateralized to the hemisphere contralateral to the movement (Van der Kamp et al., 1995). Deuschl et al. also showed significant diminution of NS' over the central area contralateral to the movement in patients with writer's cramp (Deuschl et al., 1995). These MRCP studies suggest impaired activation of the sensorimotor cortex contralateral to the affected hand just before making a voluntary movement, regardless of the kind of dystonia.
Since patients with dystonia suffer from sustained, abnormal muscle contraction during voluntary actions, a disturbance of an inhibitory mechanism of motor output has been proposed in this condition. Transcranial magnetic stimulation (TMS) enabled us to evaluate both excitatory and inhibitory functions of the corticospinal tracts (Barker et al., 1985; Mills, 1988; Kujirai et al., 1993; Wassermann et al., 1993). The physiological corticocortical and corticospinal connections for voluntary inhibition of muscles are still unclear even in normal subjects, but the fact that the pathological process in motor neuron disease differentially influences the inhibitory and excitatory motor effects of TMS suggests that different corticospinal pathways may mediate these two types of responses in human (Triggs et al., 1992). In patients with dystonia, an abnormality of the silent period evoked by TMS has been reported (Mavroudakis et al., 1995), suggesting an impairment of not only excitatory but also inhibitory corticospinal pathways. In addition, paired magnetic stimulation given to the motor cortex contralateral to the affected hand in patients with focal dystonia also showed a decrease in the early corticocortical suppression which, in normal subjects, is usually seen when tested with short interstimulus intervals (Ridding et al., 1995) as well as with relatively longer interstimulus intervals (Rona et al., 1998). Furthermore, by also using TMS in patients with cervical dystonia (Odegren et al., 1997) and in a patient with dystonia secondary to a putaminal lesion (Hanajima et al., 1994), a disturbance of the cortical inhibitory regulation of neuronal excitability was demonstrated. However, these stimulation studies have not addressed directly the mechanism underlying voluntary inhibition of muscle contraction (muscle relaxation task in the present study) in focal dystonia.
Some of the present authors studied MRCP preceding voluntary relaxation of hand muscle in normal subjects, and compared it with that preceding a similar movement, caused by muscle contraction (Terada et al., 1995). There was no significant difference in the MRCPs with respect to the waveform and scalp distribution between voluntary relaxation and active contraction of the hand muscle (Terada et al., 1995). Taking into account the results of subdural recording of MRCP associated with muscle contraction in epileptic patients (Neshige et al., 1988; Ikeda et al., 1992), the above findings were interpreted to suggest that the primary sensorimotor cortex (SI–MI) and supplementary motor area (SMA) are also active before voluntary muscle relaxation. In our recent subdural recording, the MRCP preceding voluntary muscle relaxation was clearly observed in the SMA, similarly to that preceding voluntary muscle contraction (Yazawa et al., 1998). Therefore, in the present study, we aimed at clarifying the pathophysiological mechanism underlying muscle relaxation in patients with focal hand dystonia, by recording the MRCP preceding voluntary relaxation of the hand muscle.
|
Material and methods |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
Patients
Nine patients (five men and four women) with focal dystonia of the right hand, mainly complaining of difficulty in writing, participated in this study. They were divided into two groups according to previous studies (Sheehy and Marsden, 1982
; Kaji et al., 1995b). The symptoms in three of the patients appeared only at the time of writing (simple writer's cramp), and in the remaining six patients symptoms occurred both on writing and in association with other hand tasks (dystonic writer's cramp). The mean age of the patients was 32.2 years (SD 7.2 years) and the mean duration of illness was 4.1 years. For the present study, we excluded patients older than 40 years in order to avoid a possible ageing effect (Barrett et al., 1986). All patients originally were right-handed, but one patient had acquired left hand writing before this experiment. No patient had other neurological disorders. All patients and control subjects gave informed consent after a full explanation of the purpose of this study. The study was approved by the Ethics Committee of Kyoto University School of Medicine. The electrophysiological data obtained were compared with those obtained from 10 normal subjects [eight men and two women, mean age 30.3 years (SD 6.2 years), seven right-handed and one left-handed] who had been studied previously by the authors' group, using exactly the same methods (Terada et al., 1995).
Movement paradigms
Subjects were seated in a reclining arm chair in a quiet room with their eyes kept open and fixating forward at the target placed 1.5 m in front of them during the recording session. Each subject performed two motor tasks: `relaxation' and `contraction' with the right hand (affected side in all patients) according to the previously described method (Terada et al., 1995). In the relaxation task, the right forearm was put on a paper board placed on the arm rest of the chair, with the hand pronated palm downwards. The subject was requested to keep the right wrist in extension to 20–30° for at least 5 s before each movement task, and then to let it drop by voluntarily terminating the contraction of the wrist extensor muscle. Once the relaxation was achieved, the subject maintained the relaxed position for at least 5 s and then resumed the extended position of the wrist for the next trial. Before data acquisition, all subjects practised the task so that the surface EMG activity was restricted only to the extensor carpi radialis muscle or in some cases to the extensor carpi radialis and the flexor carpi ulnaris throughout the extended position. As in the previous study (Terada et al., 1995), the polygraphic surface EMG was monitored to ensure that the hand had dropped without associated contraction of any muscles in either the affected or unaffected hand (Fig. 1). During the initial training phase for the affected hand, some contraction of the flexor carpi ulnaris muscle was seen in association with the hand drop (underlined in Fig. 1). In the training session for the unaffected hand, eight out of nine subjects were able to relax voluntarily the extensor carpi radialis muscle satisfactorily, even without training. Since one subject constantly showed additional EMG activity in the flexor carpi ulnaris and triceps brachii muscles during the relaxation task in the movement of the dystonic and the intact hand, his data were excluded from further analysis.
|
In the contraction task, the forearm was placed perpendicular to the paper board, with the ulnar side down. The subject flexed the wrist by voluntarily contracting the wrist flexor muscle as quickly as possible, and kept the flexed position for >5 s. Then, the wrist was returned to the relaxed, neutral position for the next trial. Although, in the previous study of normal subjects (Terada et al., 1995
), the degree of wrist flexion was controlled to 20–30°, some patients in the present study could not control it to a consistent degree, and they tended to flex the wrist to an excessive degree. For the repetition rate, the subjects were instructed so that the rate for the contraction task was kept the same as for the relaxation. Each recording session consisted of 50 trials of the same task, and each patient underwent three sessions each for the relaxation and contraction tasks, which were carried out in a counterbalanced order across the subjects. The task performance was monitored and stored by a video camera system, as were the EMG recordings (see below).
Data acquisition
For recording EEGs, 11 Ag/AgCl shallow cup electrodes (F3, Fz, F4, C3, C1, Cz, C2, C4, P3, Pz and P4) (American EEG Society, 1992) were fixed to the scalp with collodion, and all electrodes were referenced to linked earlobe electrodes. EOG was monitored simultaneously by an Ag/AgCl cup electrode placed at the right inferior lateral canthus referenced to the right earlobe electrode. The impedance of all electrodes was kept < 5 k
. The bandpass filter was set to 0.05–100 Hz for both EEGs and EOGs.
In order to monitor the contraction and relaxation of the corresponding muscle as well as to detect concomitant contraction of other muscles, if any, EMGs were recorded by a pair of Ag/AgCl cup electrodes placed 3 cm apart on the skin overlying each of the extensor carpi radialis, flexor carpi ulnaris, biceps brachii and triceps brachii muscles, all bilaterally (Fig. 1). The bandpass filter for recording EMGs was set to 20–100 Hz.
To determine the movement onset, an accelerometer (AS-2GA, Kyowa Electronic Instruments, Co.) was fixed to a light paper plate which was bound on the dorsal aspect of digits II–V by tapes. The low frequency filter was set to 0 Hz (DC), and the high frequency filter to 100 Hz. The accelerogram was rectified and used to obtain the fiducial point for averaging the EEG and EOG as described below.
All segments of the amplified signals covering 2.4 s before and 1.2 s after the movement onset were stored on a computer (DP1100, NEC San-Ei) at a sampling rate of 333 Hz for the subsequent off-line analysis.
Data analysis
After completing all sessions for each subject, the EEG, EOG, EMG and accelerogram for each trial were displayed on a cathode ray tube monitor, and the precise onset of the movement was determined visually on the rectified accelerogram. If there was any artefact caused by eye movements or other sources, or if EMG activities in inappropriate muscles were recognized, that trial was eliminated from further analysis.
After confirming the reproducibility of the averaged waveforms among different sessions of the same movement task, a group average for each task was obtained with respect to the movement onset for each subject. Then, a grand average for each task was obtained by averaging the group average data of like sessions across all subjects. The baseline was corrected by subtracting the average value of the initial 166 points (499 ms) from the waveform for each channel.
The onset of the slow negative pre-movement shift, which was defined as the time when the baseline began deflecting toward negativity at electrode Cz, was determined visually. In several subjects, we could not distinguish subcomponents of the MRCP due to a poor signal-to-noise ratio. In addition, some patients showed a different time course of negativity at around the time of the movement onset (corresponding to the NS' component) between the two tasks. Therefore, to simplify the interpretation of the results and to exclude the experimenter's bias, we measured the amplitude of MRCPs just at the movement onset from the baseline in all subjects, and in the Results we call this pre-movement potential shift the BP. Thus, this represents an overall cerebral activity of the preparatory/executive process for movement. In addition, to investigate the post-movement cerebral processing of each movement, the peak time of MRCP immediately after the movement onset (motor potential; MP) and its amplitude from the baseline were measured at the electrode where the negativity was maximal (C1 or Cz) for each subject. Actually, the MP amplitude was obtained by subtracting the BP amplitude measured at the movement onset from the amplitude measured at the peak time of MP. For control, the data from normal subjects (Terada et al., 1995) were re-analysed by using exactly the same method as used for the present patient group. Afterwards, statistical analysis was done in each group by using analysis of variance (ANOVA) with repeated measures design with two factors [electrode position (Electrode) and task effect (Task)]. Within each group, a paired t-test was applied to compare the BP amplitudes at each electrode between the two tasks.
In order to compare the distribution of BP between the two tasks for each group by cancelling out the effect of absolute amplitude difference, the data were normalized by dividing the values measured at all electrodes by the maximal BP amplitude for each task for each individual subject. Then, repeated measures mixed type ANOVA was adopted with three factors [within-group factors: Electrode and Task, between-group factor: effect of disease (Disease)]. To investigate the horizontal distribution of BP over the central area, the above procedure was applied to five selected central electrodes (C3, C1, Cz, C2 and C4). In order to compare the normalized BP amplitude at each electrode between the two groups, separate one-way ANOVA was adopted for each task. The significance of degrees of freedom for all repeated measure analysis was evaluated by using Greenhouse–Geisser correction.
|
Results |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
On task performance, all the patients with focal hand dystonia studied here reported that the contraction task was more difficult to perform than the relaxation task. This was opposite to the situation in the normal controls; they found the relaxation task more difficult than the contraction (Terada et al., 1995
).
Muscle relaxation versus contraction in focal dystonia
In the patient group, there was no difference in the BP onset time between the two tasks [F(1,7) = 4.67, P = 0.67] (Table 1). The amplitude of BP in the contraction task was maximal at the left central area (C1) (6.22 ± 3.31 µV) and predominantly distributed over the left hemisphere (Figs 2 and 3). In the relaxation task, the BP was maximal at the midline central area (Cz) (4.37 ± 1.71 µV) and was almost symmetrically distributed (Figs 2 and 3). The BP appeared larger on the right hemisphere in the frontal and parietal areas, but the difference did not reach statistical significance (Fig. 3). Individually, seven out of eight subjects showed the C1 maximum in the contraction task, whereas the remaining subject showed the maximal amplitude at Cz. In the relaxation task, the BP was maximal at Cz in all subjects. ANOVA did not disclose a main effect of Task [F(1,7) = 4.76, 
= 1.00, P = 0.07], but significant interactions between the two factors were present [Task x Electrode: F(10,70) = 3.60, = 0.22, P < 0.05). Significant amplitude difference was observed at the left central (C1 and C3) and the left parietal (P3) region (P < 0.05, paired t-test); the BP amplitudes at those electrodes were lower in the relaxation task than in the contraction task (Fig. 3). Therefore, the interaction can be explained by the amplitude diminution over the left hemisphere in the relaxation task.
|
|
|
The MP peak time showed no significant difference between the two tasks (P = 0.76, paired t-test) (Table 2
). The MP amplitude was maximal at C1 (–2.38 ± 0.95 µV) in the contraction task and at Cz (–3.73 ± 2.72 µV) in the relaxation task. In both tasks, it was distributed predominantly over the frontocentral area. ANOVA disclosed neither Task effect [F(1,7) = 1.29, = 1.00, P = 0.29] nor Electrode interaction [F(10,70) = 1.53, = 0.25, P = 0.24] for the MP amplitude, suggesting that the MP in focal hand dystonia was not affected by the task in terms of peak time, amplitude and potential distribution.
|
Muscle relaxation versus contraction in the control group
In the normal control group, BP started symmetrically and became maximal at C1 just before the movement onset in both tasks (3.63 ± 1.66 µV in the contraction and 4.37 ± 1.71 µV in the relaxation) (Fig. 4
). As reported previously, there was a significant difference in the onset latency of BP between the two tasks [F(1,9) = 11.99, P < 0.01; Table 1
]. As for the individual analysis, in the contraction task, five out of the 10 subjects showed the C1 maximum, three Cz and the remaining two C3. In the relaxation task, half of the subjects showed the C1 maximum, four Cz and one C3.
|
In comparing the two tasks within the normal control group, there was no Task effect [F(1,9) = 1.53,
= 1.0, P = 0.25], but there was a significant interaction between the two factors [Task x Electrode: F(10,90) = 4.12, =0.39, P < 0.01]. This interaction was caused by the general increase of BP amplitude (especially in the parietal area) in the relaxation task, but only P3 showed a significant difference (P < 0.05, paired t test).
The MP peak time was significantly earlier with respect to the movement onset in the contraction task than in the relaxation task (P < 0.01, paired t test) (Table 2). The MP amplitude was maximal at C1 in both tasks (contraction, –3.15 ± 1.61 µV; relaxation, –3.56 ± 2.84 µV) with predominantly frontocentral distribution. ANOVA disclosed neither Task effect [F(1,9) = 0.41, = 1.00, P = 0.54] nor Electrode interaction [F(10,90) = 0.34, = 0.19, P = 0.76] for the MP amplitude.
Focal dystonia versus control
There was no significant difference in the onset time of BP between the two groups for either task [relaxation: F(1,16) = 0.08, P = 0.79, contraction: F(1,16) = 1.61, P = 0.22] (Table 1). When comparing the amplitude values of BP at all electrodes, ANOVA with three factors disclosed only a main effect of the Electrode [F(10,160) = 18.89, = 0.22, P < 0.001], and this effect was not affected by Disease [F(10,160) = 2.89, = 0.22, P < 0.19]. The interaction of the factors (Task x Electrode x Disease) was not significant [F(10,160) = 2.07, = 0.35, P = 0.07].
ANOVA at the five central channels showed significant interaction of the factors [Task x Electrode x Disease: F(4, 4) = 4.42, = 0.61, P < 0.05]. This indicates that the normalized BP distribution at the central area was significantly influenced by the two factors (Task and Disease).
A separate ANOVA comparing the normalized amplitude values at each electrode in the two groups for each task disclosed the significant difference at C1 and C3 in the relaxation task; they were smaller in the patient group than in the control group (Fig. 5). In the contraction task, however, the differences appeared at C2 and C4 (the central area ipsilateral to the movement), and the normalized amplitude at those electrodes was larger in the patient group than in the normal controls (Fig. 5).
|
The MP peak time was significantly affected by Disease [(F(1,16) = 8.39, P < 0.02]. The difference between the groups was found only in the relaxation task, i.e. the MP peak time in the relaxation task in focal hand dystonia was significantly earlier with respect to the movement onset than that in controls (Table 2
). However, the MP amplitude and scalp distribution were not influenced by Disease [Task x Electrode x Disease: F(10,160) = 1.22, P = 0.31]. |
Discussion |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
This study was aimed mainly at elucidating how the cortical mechanism underlying the preparation for voluntary hand muscle relaxation was affected in focal hand dystonia. The main finding was a diminished amplitude of the slow pre-movement shift (BP) preceding voluntary relaxation of the right (affected) hand muscle over the left central area in the patients. In the study of normal subjects employing exactly the same methods, the authors' group previously reported that the slow potentials preceding voluntary, self-paced relaxation and contraction of the right hand muscle were quite similar to each other in terms of the waveform and scalp distribution (Terada et al., 1995
). Taking into account the results of subdural recording of MRCPs associated with muscle contraction in epilepsy patients, which suggested the SI–MI and SMA as the main generator sources (Neshige et al., 1988; Ikeda et al., 1992), it was postulated that the potential preceding the muscle relaxation might represent excitatory postsynaptic potentials of either corticospinal neurons projecting to the spinal inhibitory neuron or inhibitory interneurons in the SI–MI and/or SMA (Terada et al., 1995). If this assumption is correct, the smaller BP at the contralateral central area in the relaxation task compared with the contraction task might suggest the impaired activation of these inhibitory motor systems in the contralateral SI–MI in focal hand dystonia patients. An abnormality of the cortical inhibitory motor system in focal hand dystonia was reported by using TMS applied to the motor cortex; the motor evoked potential was less inhibited by a conditioning stimulus of subthreshold intensity in focal hand dystonia compared with normal controls, although there was no difference in the threshold of motor evoked potential at rest between focal hand dystonia and the controls (Ridding et al., 1995).
The presence of a cortical inhibitory system projecting to the spinal motor neuron was demonstrated in primates by Schmidt and McIntosh (Schmidt and McIntosh, 1990). They explored the neuronal function in the precentral gyrus in monkeys by using intracortical microstimulation. By giving trains of microstimuli to cells in the precentral gyrus, abrupt inhibition or contraction of the forearm muscle was elicited, as in the TMS study in human, and such inhibitory cells were scattered among the excitatory cells in the precentral gyrus. An inhibitory effect of the stimuli on such cells was observed similarly during voluntary movement and during muscle activation caused by vibration. It suggested the possibility that the motor cortex might contain a neuronal population which caused spinal presynaptic inhibition by activating inhibitory interneurons in the spinal cord (Schmidt and McIntosh, 1990). Moreover, they found that in certain regions just adjacent to the area showing inhibition, the microstimulation caused an excitation in both extensor and flexor muscles (co-contraction). In other regions, the stimuli produced excitation of one extensor muscle and inhibition of another extensor muscle, or excitation of a flexor muscle and simultaneous inhibition of another flexor muscle. If such inhibitory cells are functionally impaired in humans, presumably as the result of the deficient control from basal ganglia, a dystonic symptom might occur, and an abnormal MRCP as shown in the present study might reflect the impaired function of the inhibitory motor preparatory systems.
Previous MRCP studies employing muscle contraction in various dystonic patients also disclosed an abnormal distribution of BP, i.e. a diminished amplitude of the pre-movement potential over the central area contralateral to the movement (Fève et al., 1994; Deuschl et al., 1995; Van der Kamp et al., 1995). However, we did not observe such specific diminution of BP in the patients with focal hand dystonia, at least preceding the voluntary muscle contraction task (Figs 2 and 3). In fact, both the focal hand dystonia and control groups showed the maximal amplitude of BP at the contralateral central area in the contraction task and, in the ipsilateral central area, the normalized amplitude of BP was even larger in focal hand dystonia than in the controls. The absence of laterality can be interpreted as a loss of dominance which is normally seen in unilateral movement, and it suggests a functional impairment of the contralateral SI–MI in focal hand dystonia. It is in good agreement with the results of previous studies (Fève et al., 1994; Deuschl et al., 1995; Van der Kamp et al., 1995). First, the different degree of effort needed to perform the contraction task in the present focal hand dystonia group and in the reported patients should be taken into account to explain the differences. All the previous studies employed easy, phasic, brisk movements of the finger or wrist, whereas our contraction task required the patients to keep the flexed wrist position for as long as 5 s. In fact, some patients could not control the magnitude of wrist flexion to an appropriate level, i.e. they tended to make an excessive contraction compared with normal controls. It has been shown that when a complex task is employed, the BP loses its contralateral dominance just before the movement onset, probably because the SI–MI becomes active bilaterally as the complexity increases (Benecke et al., 1985; Simonetta et al., 1991; Kitamura et al., 1993; Shibasaki et al., 1993). Therefore, the great effort made by the patients in the present contraction task might have obscured the abnormality of the absolute BP amplitude that was found in the previous studies.
Furthermore, the analysis method employed in the present study was different from that used in the previous ones. Those previous studies selectively measured a subcomponent of pre-movement potentials (NS') which appears immediately before the movement onset, but we analysed the whole pre-movement activity measured from the baseline at the movement onset. In the present study, the waveform of the NS' component for each task varied among the patients, probably due to a smaller number of acceptable trials (poor signal-to-noise ratio). Therefore, in order to avoid any arbitrary subdivision of BP into NS1 and NS2, we used the amplitude of MRCP measured at the movement onset as an indicator of movement preparation and/or execution. It may be another cause which masks any significant difference in the present results of the contraction task between the two groups.
The neostriatum, especially the putamen, is regarded as the structure responsible for dystonia (Fross et al., 1987; Lorenzana et al., 1992; Hallett, 1993). Hallett proposed that the involuntary movement in dystonia could be explained by overactivity of the direct pathway via the globus pallidus pars interna/substantia nigra pars reticulata (Hallett, 1993). However, based on the studies of Parkinson's disease, the question as to whether the BP is affected by basal ganglia disorder or not still remains unsolved (Deecke et al., 1977; Barrett et al., 1986; Dick et al., 1989; Ikeda et al., 1997). In contrast to Parkinson's disease, the results of the studies of BP in focal hand dystonia seem consistent among the few different studies reported so far (Fève et al., 1994; Deuschl et al., 1995; Van der Kamp et al., 1995). Although the interaction of the SMA/SI–MI and basal ganglia in the generation of BP is still unclear, the generating mechanism of BP in the two basal ganglia disorders, Parkinson's disease and focal hand dystonia, seems to be different. In patients with Parkinson's disease, a PET activation study using H215O showed poor activation in the SMA and dorsolateral prefrontal cortex, but activation in the SI–MI was preserved, and was as much as in the normal controls (Playford et al., 1992; Brooks, 1997; Samuel et al., 1997). In contrast, activation in both the caudal part of the SMA and the SI–MI was diminished in patients with focal hand dystonia (Tempel and Perlmutter 1993; Ceballos-Baumann et al., 1995). These findings suggest that inconsistent results of MRCP in Parkinson's disease may be due, at least partly, to the relatively preserved activity of the SI–MI in the patients with Parkinson's disease. Thus, the present results in focal hand dystonia are consistent with those of the previous MRCP and PET studies, and we postulate that basal ganglia function can influence the findings of MRCP in different ways in Parkinson's disease and focal hand dystonia. According to a recent hypothesis, basal ganglia do not necessarily generate movements, but they act broadly to inhibit the competing motor mechanisms that would otherwise interfere with the desired movement (see review by Mink, 1996). A PET study showed a decreased dopaminergic activity in the putamen in patients with focal dystonia (Perlmutter et al., 1991, 1997a). Furthermore, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated baboons showed transient unilateral dystonic symptoms followed by permanent parkinsonism (Perlmutter et al., 1997b). Perlmutter et al. suggested that in patients with dystonia, the impaired striatal D2 activity may cause diminished activity of an indirect pathway of the basal ganglia and subsequent disfacilitation of thalamocortical projections to the MI and SMA (Perlmutter et al., 1997b).
One of the clinical characteristics of focal hand dystonia is task-specificity. Byl et al. reported a primate model of focal dystonia, in which a rapid, repetitive, daily behavioural hand movement task caused remapping of the somatotopic representation of the somatosensory cortex (Byl et al., 1996). Based on neurophysiological evidence, including abnormal responses to a peripheral vibratory stimulus (Tempel and Perlmutter 1990, 1993; Kaji et al., 1995b), the possibility of abnormal sensory processing in patients with dystonia was proposed (Hallett, 1995). In the paradigm employed in the present study, the relaxation always had to be preceded by muscle contraction. Therefore, this condition might have some effect similar to vibration on the sensory cortex, by means of activation of muscle afferent pathways. If that is the case, it is reasonable to postulate that the abnormal sensory processing in dystonia is partly responsible for impaired MRCP in our relaxation paradigm. Since the recording of MRCPs requires the cooperation of the subject for an extended period, the present study in the patient group did not take the task-specificity into account. Further study aimed at the elucidation of this mechanism is warranted.
In the present study, we also examined the post-movement activity. We found a different MP peak time in the two groups in the relaxation task. The MP determined at the central electrodes in the present study seems to be closely related to the frontal peak of MP reported in the previous study in terms of its peak time (Terada et al., 1995). The previous study explained, based on the findings of the accelerograms, that the different peak time of the fpMP in the two tasks in normal subjects was probably caused by jittering of the relaxing speed of the hand muscles. This might also hold true for the comparison between focal hand dystonia and controls in the present study. As shown in Figs 2 and 4, the accelerograms in the relaxation task showed a lesser degree of jittering in the focal hand dystonia group compared with the control group. In addition, the peak time of the MP seems to be very close to the peak of the accelerogram. Post-movement activities of the MRCP seem to reflect kinaesthetic input from the peripheral nervous system (Tarkka and Hallett, 1991), and subdural recording of the MRCP showed that a major post-movement component was generated in the primary somatosensory cortex (Ikeda et al., 1995). It is postulated further that the post-movement sensory processing in the relaxation task in focal hand dystonia is different from that in controls, as recently suggested (Hallett, 1995). The delayed peak time of MPs in the relaxation task might suggest that the post-movement cerebral processing in this condition might require more steps compared with the contraction task. However, it is difficult to reach any conclusion in this regard based only on the present results, and further studies are warranted to unravel this particular issue.
|
Acknowledgments |
|---|
The authors wish to thank Miss N. Samura for technical assistance in data acquisition. This study was partly supported by Grants-in-Aid for Scientific Research (A) 09308031, (A) 08670705 and (C) 10670583, and on Priority Areas 08279106 from the Japan Ministry of Education, Science, Sports and Culture, and a Research Grant for the Future Program JSPS-RFTF97L00201 from the Japan Society for the Promotion of Science.
|
References |
|---|
|
TopAbstractIntroductionMaterial and methodsResultsDiscussionReferences |
|---|
Barker AT, Jalinous R, Freeston IL. Non-invasive magnetic stimulation of human motor cortex [letter]. Lancet 1985; 1: 1106–7.[Web of Science][Medline]
Barrett G, Shibasaki H, Neshige R. Cortical potential shifts preceding voluntary movement are normal in parkinsonism. Electroencephalogr Clin Neurophysiol 1986; 63: 340–8.[Web of Science][Medline]
Benecke R, Dick JP, Rothwell JC, Day BL, Marsden CD. Increase of the Bereitschaftspotential in simultaneous and sequential movements. Neurosci Lett 1985; 62: 347–52.[Web of Science][Medline]
Brooks DJ. Motor disturbance and brain functional imaging in Parkinson's disease. [Review]. Eur Neurol 1997; 38 Suppl 2: 26–32.
Byl NN, Merzenich MM, Jenkins WM. A primate genesis model of focal dystonia and repetitive strain injury: I. Learning-induced dedifferentiation of the representation of the hand in the primary somatosensory cortex in adult monkeys. Neurology 1996; 47: 508–20.
Ceballos-Baumann AO, Passingham RE, Warner T, Playford ED, Marsden CD, Brooks DJ. Overactive prefrontal and underactive motor cortical areas in idiopathic dystonia. Ann Neurol 1995; 37: 363–72.[Web of Science][Medline]
Ceballos-Baumann AO, Sheean G, Passingham RE, Marsden CD, Brooks DJ. Botulinum toxin does not reverse the cortical dysfunction associated with writer's cramp. A PET study. Brain 1997; 120: 571–82.
Deecke L, Englitz HG, Kornhuber HH, Schmitt G. Cerebral potentials preceding voluntary movement in patients with bilateral or unilateral Parkinson akinesia. In: Desmedt JE, editor. Attention, voluntary contraction and event-related cerebral potentials. Progress in clinical neurophysiology, Vol. 1. Basel: S. Karger; 1977. p. 151–63.
Deuschl G, Toro C, Matsumoto J, Hallett M. Movement-related cortical potentials in writer's cramp [see comments]. Ann Neurol 1995; 38: 862–8. Comment in: Ann Neurol 1995; 38: 837–8.[Web of Science][Medline]
Dick JP, Rothwell JC, Day BL, Cantello R, Buruma O, Gioux M, et al. The Bereitschaftspotential is abnormal in Parkinson's disease. Brain 1989; 112: 233–44.
Fahn S. Concept and classification of dystonia. [Review]. Adv Neurol 1988; 50: 1–8.[Medline]
Fève A, Bathien N, Rondot P. Abnormal movement related potentials in patients with lesions of basal ganglia and anterior thalamus. J Neurol Neurosurg Psychiatry 1994; 57: 100–4.
Fross RD, Martin WRW, Li D, Stoessl AJ, Adam MJ, Ruth TJ, et al. Lesions of the putamen: their relevance to dystonia. Neurology 1987; 37: 1125–9.
Hallett M. Physiology of basal ganglia disorders: an overview. [Review]. Can J Neurol Sci 1993; 20: 177–83.[Web of Science][Medline]
Hallett M. Is dystonia a sensory disorder? [editorial]. Ann Neurol 1995; 38: 139–40.[Web of Science][Medline]
Hanajima R, Ugawa Y, Masuda N, Kanazawa I. Changes of motor cortical excitability in a patient with unilateral focal dystonia due to a lesion of the contralateral putamen [abstract]. Mov Disord 1994; 9 Suppl 1: 43.
Ikeda A, Lüders HO, Burgess RC, Shibasaki H. Movement-related potentials recorded from supplementary motor area and primary motor area. Brain 1992; 115: 1017–43.
Ikeda A, Lüders HO, Burgess RC, Sakamoto A, Klem GH, Morris HH 3rd, et al. Generator locations of movement-related potentials with tongue protrusions and vocalizations: subdural recording in human [published erratum appears in Electroencephalogr Clin Neurophysiol 1995; 96: 484]. Electroencephalogr Clin Neurophysiol 1995; 96: 310–28.[Medline]
Ikeda A, Shibasaki H, Kaji R, Terada K, Nagamine T, Honda M, et al. Abnormal sensorimotor integration in writer's cramp: study of contingent negative variation. Mov Disord 1996; 11: 683–90.[Web of Science][Medline]
Ikeda A, Shibasaki H, Kaji R, Terada K, Nagamine T, Honda M, et al. Dissociation between contingent negative variation (CNV) and Bereitschaftspotential (BP) in patients with parkinsonism. Electroencephalogr Clin Neurophysiol 1997; 102: 142–51.[Web of Science][Medline]
Kaji R, Ikeda A, Ikeda T, Kubori T, Mezaki T, Kohara N, et al. Physiological study of cervical dystonia. Task-specific abnormality in contingent negative variation. Brain 1995a; 118: 511–22.
Kaji R, Rothwell JC, Katayama M, Ikeda T, Kubori T, Kohara N, et al. Tonic vibration reflex and muscle afferent block in writer's cramp. Ann Neurol 1995b; 38: 155–62.[Web of Science][Medline]
Karbe H, Holthoff VA, Rudolf J, Herholz K, Heiss WD. Positron emission tomography demonstrates frontal cortex and basal ganglia hypometabolism in dystonia. Neurology 1992; 42: 1540–4.
Kitamura J, Shibasaki H, Takagi A, Nabeshima H, Yamaguchi A. Enhanced negative slope of cortical potentials before sequential as compared with simultaneous extensions of two fingers. Electroencephalogr Clin Neurophysiol 1993; 86: 176–82.[Web of Science][Medline]
Kornhuber HH, Deecke L. Hirnpotentialänderungen bei Wilkürbewegungen und passiven Bewegungen des Menschen: Bereitschaftspotential und reafferente Potentiale. Pflügers Arch 1965; 284: 1–17.
Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, et al. Corticocortical inhibition in human motor cortex. J Physiol (Lond) 1993; 471: 501–19.
Lorenzana L, Cabezudo JM, Porras LF, Polaina M, Rodriguez-Sanchez JA, Garcia-Yague LM. Focal dystonia secondary to cavernous angioma of the basal ganglia: case report and review of the literature [see comments]. [Review]. Neurosurgery 1992; 31: 1108–11. Comment in: Neurosurgery 1993; 32: 1056.[Web of Science][Medline]
Mavroudakis N, Caroyer JM, Brunko E, Zegers de Beyl D. Abnormal motor evoked responses to transcranial magnetic stimulation in focal dystonia. Neurology 1995; 45: 1671–7.
Mills KR. Excitatory and inhibitory effects on human spinal motoneurones from magnetic brain stimulation. Neurosci Lett 1988; 94: 297–302.[Web of Science][Medline]
Mink JW. The basal ganglia: focused selection and inhibition of competing motor programs. [Review]. Prog Neurobiol 1996; 50: 381–425.[Web of Science][Medline]
Neshige R, Lüders H, Shibasaki H. Recording of movement-related potentials from scalp and cortex in man. Brain 1988; 111: 719–36.
Odergren T, Iwasaki N, Borg J, Forssberg H. Impaired sensory–motor integration during grasping in writer's cramp. Brain 1996; 119: 569–83.
Odergren T, Rimpiläinen I, Borg J. Sternocleidomastoid muscle responses to transcranial magnetic stimulation in patients with cervical dystonia. Electroencephalogr Clin Neurophysiol 1997; 105: 44–52.[Medline]
Oppenheim H. Uber eine eigenartige Krampfkrankenheit des kindlichen und jugendlichen Alters (Dysbasia lordotica progressiva, Dystonia musculorum deformans). Neurol Zentralbl 1911; 30: 1090–107.
Perlmutter JS, Moerlein SM, Huang D-R, Todd RD. Non-steady-state measurement of in vivo radioligand binding with positron emission tomography: specificity analysis and comparison with in vitro binding. J Neurosci 1991; 11: 1381–9.[Abstract]
Perlmutter JS, Stambuk MK, Markham J, Black KJ, McGee-Minnich L, Jankovic J, et al. Decreased [18F]spiperone binding in putamen in idiopathic focal dystonia. J Neurosci 1997a; 17: 834–50.
Perlmutter JS, Tempel LW, Black KJ, Parkinson D, Todd RD. MPTP induces dystonia and parkinsonism. Clues to the pathophysiology of dystonia. Neurology 1997b; 49: 1432–8.
Playford ED, Jenkins IH, Passingham RE, Nutt J, Frackowiak RS, Brooks DJ. Impaired mesial frontal and putamen activation in Parkinson's disease: a positron emission tomography study. Ann Neurol 1992; 32: 151–61.[Web of Science][Medline]
Ridding MC, Sheean G, Rothwell JC, Inzelberg R, Kujirai T. Changes in the balance between motor cortical excitation and inhibition in focal, task specific dystonia. J Neurol Neurosurg Psychiatry 1995; 59: 493–8.
Rona S, Berardelli A, Vacca L, Inghilleri M, Manfredi M. Alterations of motor cortical inhibition in patients with dystonia. Mov Disord 1998; 13: 118–24.[Web of Science][Medline]
Samuel M, Ceballos-Baumann AO, Blin J, Uema T, Boecker H, Passingham RE, et al. Evidence for lateral premotor and parietal overactivity in Parkinson's disease during sequential and bimanual movements. A PET study [see comments]. Brain 1997; 120: 963–76. Comment in: Brain 1998; 121: 769–72.
Schmidt EM, McIntosh JS. Microstimulation mapping of precentral cortex during trained movements. J Neurophysiol 1990; 64: 1668–82.
Sheehy MP, Marsden CD. Writer's cramp—a focal dystonia. Brain 1982; 105: 461–80.
Shibasaki H, Shima F, Kuroiwa Y. Clinical studies of the movement-related cortical potential (MP) and the relationship between the dentatorubrothalamic pathway and readiness potential (RP). J Neurol 1978; 219: 15–25.[Web of Science][Medline]
Shibasaki H, Barrett G, Halliday E, Halliday AM. Components of the movement-related cortical potential and their scalp topography. Electroencephalogr Clin Neurophysiol 1980; 49: 213–26.[Web of Science][Medline]
Shibasaki H, Sadato N, Lyshkow H, Yonekura Y, Honda M, Nagamine T, et al. Both primary motor cortex and supplementary motor area play an important role in complex finger movement. Brain 1993; 116: 1387–98.
Simonetta M, Clanet M, Rascol O. Bereitschaftspotential in a simple movement or in a motor sequence starting with the same simple movement. Electroencephalogr Clin Neurophysiol 1991; 81: 129–34.[Web of Science][Medline]
Tarkka IM, Hallett M. Topography of scalp-recorded motor potentials in human finger movements. J Clin Neurophysiol 1991; 8: 331–41.[Web of Science][Medline]
Tempel LW, Perlmutter JS. Abnormal vibration-induced cerebral blood flow responses in idiopathic dystonia. Brain 1990; 113: 691–707.
Tempel LW, Perlmutter JS. Abnormal cortical responses in patients with writer's cramp [published erratum appears in Neurology 1994; 44: 2411]. Neurology 1993; 43: 2252–7.
Terada K, Ikeda A, Nagamine T, Shibasaki H. Movement-related cortical potentials associated with voluntary muscle relaxation. Electroencephalogr Clin Neurophysiol 1995; 95: 335–45.[Web of Science][Medline]
Triggs WJ, Macdonell RA, Cros D, Chiappa KH, Shahani BT, Day BJ. Motor inhibition and excitation are independent effects of magnetic cortical stimulation. Ann Neurol 1992; 32: 345–51.[Web of Science][Medline]
Van der Kamp W, Rothwell JC, Thompson PD, Day BL, Marsden CD. The movement-related cortical potential is abnormal in patients with idiopathic torsion dystonia [published erratum appears in Mov Disord 1996; 11: 118]. Mov Disord 1995; 10: 630–3.[Web of Science][Medline]
Wassermann EM, Pascual-Leone A, Valls-Solé J, Toro C, Cohen LG, Hallett M. Topography of the inhibitory and excitatory responses to transcranial magnetic stimulation in a hand muscle. Electroencephalogr Clin Neurophysiol 1993; 89: 424–33.[Web of Science][Medline]
Yazawa S, Ikeda A, Kunieda T, Mima T, Nagamine T, Ohara S, et al. Supplementary motor area is active in preparation for both voluntary muscle relaxation and contraction: subdural recording of Bereitschaftspotential. Neurosci Lett 1998; 244: 145–8.[Web of Science][Medline]
Received February 1, 1999. Accepted March 2, 1999.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Oga, M. Honda, K. Toma, N. Murase, T. Okada, T. Hanakawa, N. Sawamoto, T. Nagamine, J. Konishi, H. Fukuyama, et al. Abnormal cortical mechanisms of voluntary muscle relaxation in patients with writer's cramp: an fMRI study Brain, April 1, 2002; 125(4): 895 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Matsumoto, A. Ikeda, S. Ohara, T. Kunieda, K. Kimura, J. B. Takahashi, S. Miyamoto, W. Taki, N. Hashimoto, and H. Shibasaki Nonconvulsive focal inhibitory seizure: Subdural recording from motor cortex Neurology, August 8, 2000; 55(3): 429 - 431. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||