Brain, Vol. 123, No. 9, 1765-1766,
September 2000
© 2000 Oxford University Press
Editorial |
Disorder of movement preparation in dystonia
Human Motor Control Section, NINDS, National Institutes of Health Bethesda, MD, USA
Dystonia is undoubtedly characterized by a disorder of movement execution. In many patients, the `involuntary movements' are brought about entirely by attempted voluntary movement. Only in more severe cases are there truly involuntary movements, but even they are exacerbated by volition. The EMG pattern underlying movement demonstrates too much motor activation. There is excessive activation of antagonists, overflow into synergists, unnecessarily activated muscles and prolongation of muscle activation. Such activation gives rise to abnormal muscle spasms and incoordination.
A number of recent studies seem to indicate that excessive muscle activation is due to a deficiency of inhibition (Berardelli et al., 1998
; Hallett, 1998). Defective inhibition has been demonstrated at all levels of the neuraxis, spinal cord, brainstem and motor cortex. The most direct demonstration of this has been done with paired-pulse transcranial magnetic stimulation studies, which permit investigation of intracortical inhibition. The basal ganglia are in a good position, and seem anatomically able, to regulate some aspects of inhibition. Indeed, it has seemed to many investigators that the basal ganglia help to select movement by facilitating the appropriate movement and inhibiting the inappropriate ones. Then dystonia could be understood as a failure of the inhibition. The direct pathway through the basal ganglia could be the facilitation loop and the indirect pathway the inhibitory one.
While originally a surprising concept since sensation is generally thought to be normal in patients, it is now clear that there is a significant disorder of sensory function in dystonia (Hallett, 1995). Such a problem can be highly relevant to a motor disorder since a major role of the sensory system is to drive the motor system. Hence, disordered sensation can lead to disordered movement. Evidence for sensory dysfunction is now direct with experiments showing defective kinesthesia (Grunewald et al., 1997), temporal discrimination and spatial discrimination (Bara-Jimenez et al., 2000). Physiological assessment of the sensory pathway shows enlarged sensory receptive fields of thalamic neurones (Lenz et al., 1999) and disorder in the cortical sensory homunculus (Bara-Jimenez et al., 1998). There is also reduced sensory activation on functional PET scans in somatosensory cortex as well as supplementary motor cortex (SMA). The efficacy of the geste manoeuvre in many patients is direct evidence for the ability of the sensory system to affect the motor system.
Abnormalities of the N30 component of the median nerve sensory evoked potential (SEP) are relevant to the issue of sensory disturbances, and need to be commented on specifically for the discussion to follow. Virtually everything is controversial about the N30. First of all, its generator is debated. The potential is maximal frontally and is affected by lesions of frontal cortex; the SMA is often suggested as the source. Most evidence, however, suggests that it is most likely the frontal pole of a tangential dipole located in the post-central gyrus. The best evidence for this comes from direct cortical recordings. Secondly, its alterations in disease are not consistent in different reports. One of the reasons for this is that the N30 is a highly volatile potential, being very sensitive to the exact stimulation methods, the psychological state and the motor task. Diminution in amplitude of the N30 was reported in patients with Parkinson's disease, and while this has not been found by all authors, its increase in amplitude with levodopa does seem clear. Increase in its amplitude has been reported by some investigators in patients with dystonia (Berardelli et al., 1998; Hallett, 1998). While the N30 clearly represents early sensory processing and may be an indicator of sensory dysfunction in dystonia, its role is not well understood.
In addition to a movement execution disorder and a sensory disorder, it is now clear that there is also a disorder of movement preparation. Movement preparation involves a number of factors, including the process of sensorimotor integration. Past evidence for a disorder of preparation includes abnormalities in the EEG prior to a self-paced voluntary movement, including a loss of negativity of the movement-related cortical potential and a deficit of event-related desynchronization in the beta band (Toro et al., 2000). There is also an abnormality in the EEG during the waiting period for a go-signal (S2) after a warning signal (S1). The EEG during this period is called the contingent negative variation (CNV), and it is also deficient in dystonia (Hamano et al., 1999). The paper in the current issue of Brain by Murase and colleagues gives further evidence for a problem in movement preparation, showing that the N30 is not properly modulated during this time (Murase et al., 2000). The N30 is ordinarily reduced in amplitude (gated) in the premovement period as well as during the movement period. In dystonic patients there is no gating in the premovement period, while normal gating occurs during movement. This suggests faulty sensory processing that might impair the developing motor program.
This finding might give a partial explanation for why the N30 is found to be abnormally large in some studies. If the experimental set-up was such that the subjects were thinking about moving their hands, then the dystonic patients would suppress their N30 potentials less than the normal subjects.
Murase and colleagues found another abnormality in the premovement period. The P22 was gated more in the dystonic patients than in the normal control subjects. The origin of the P22 is less debated than the N30, most authorities believing it to be a radial dipole from the precentral gyrus. Hence, the P22 might reflect an aspect of motor cortex function and the N30 an aspect of sensory cortex function. At the moment, it is difficult to be more specific than that since the physiology of gating and its significance are not well understood.
Disordered preparation for movement will certainly be a factor in faulty execution. Precise processing of all sensory stimuli from the environment is relevant in designing an appropriate movement. The nervous system prefers to be anticipatory rather than reactive. Murase et al. suggest that their information helps to explain the phenomenon of the sensory trick, since the added sensation might rebalance the motor system. Whether this speculation is true or not remains to be determined, but it has already been demonstrated that the sensory trick in patients with blepharospasm will normalize the R2 of the blink reflex (Gomez-Wong et al., 1998).
References
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