Dystonia: A sensory and motor disorder of short latency inhibition

In 1995, Kaji et al. published an article in Annals of Neurology, showing, among other things, that muscle vibration in patients with focal hand dystonia (FHD) could provoke the dystonia. I wrote an editorial about that article, entitled “Is Dystonia A Sensory Disorder? ” Was it possible to consider that the primary abnormality in dystonia was sensory and that the motor manifestations were just driven by aberrant sensory signals? Since that time, there has been considerable work looking at sensory features in focal dystonia. From a behavioral point of view, while the sensory perceptual problems are mild, they are quite definite. The abnormalities are seen both for spatial discrimination and temporal discrimination. Patients with dystonia need a larger spacing to appreciate two stimuli as being separate both in the spatial and temporal domains. These abnormalities are not purely somatotopic with the type of focal dystonia. They are present in both hands of patients with unilateral FHD and even in the hands of patients with cervical dystonia and blepharospasm. The abnormalities are even present in some relatives of patients with dystonia, suggesting that they might be nonmanifesting carriers of some yet unknown gene with incomplete penetrance. From a pathophysiological point of view, the search for aberrant somatotopy was stimulated by the findings of Byl et al. in a primate model that showed enlarged and overlapped receptive fields. While the model, at least retrospectively, has many flaws, the altered somatotopy in patients was very clear. This was first demonstrated with somatosensory-evoked potential mapping and then subsequently demonstrated with functional magnetic resonance imaging (fMRI). The article in this issue by Nelson et al. further refines these observations with high-resolution fMRI mapping. Just like the behavior, the abnormal somatotopy extends well beyond the region of the particular focal dystonia. For example, the abnormality is present on the unaffected side of patients with unilateral FHD. In fact, there is some evidence that it might even be worse on the unaffected side. The underlying pathophysiology of this appears to be a loss of lateral inhibition. Ordinarily, if the median nerve somatosensory-evoked potential (SEP) and ulnar nerve SEP are produced together, the combined SEP is less that the sum of the two single SEPs. This is not true in FHD (Fig 1A, B). Recently, our group has identified the pathophysiology of the temporal discrimination abnormality using SEP recovery curves. If two SEPs are produced at short interval, components of the second SEP are inhibited by the first one. A highly-specific abnormality was seen in the patients with FHD. Only for the P27 component and only for the 5ms interval was there a loss of inhibition (Fig 1C). On the motor side, there are also a variety of abnormalities that relate to loss of inhibition. Behaviorally, there has been a longstanding idea that the overflow of movement seen with movement in FHD patients represents a loss of inhibition. There is now specific evidence that there is a loss of “surround inhibition,” a phenomenon whereby muscles not involved with the desired movement should be actively inhibited at the onset of a movement. Patients with FHD show a loss of surround inhibition with features in both in time and space. With neurophysiological tools, particularly with transcranial magnetic stimulation, it is possible to evaluate many intracortical inhibitory circuits. Patients with FHD show abnormalities in short intracortical inhibition (SICI) and long intracortical inhibition (LICI) even at rest. They also show abnormalities of SICI that correlate with, and partly explain, the abnormality of surround inhibition during movement. The data are accumulating showing abnormalities in both sensory and motor systems of short latency inhibitory mechanisms. This leads to the hypothesis that the fundamental abnormality in dystonia may well be a class or classes of inhibitory cortical interneurons. That abnormality might be primary in the sensorimotor cortex itself or the abnormality might be primary in the basal ganglia, with an abnormal influence on the sensorimotor cortex. One likely influence of the basal ganglia upon the motor cortex is to enhance surround inhibition. Relating this specifically to the finding in the current work, abnormalities in cortical inhibition should lead to overlapped and aberrantly organized receptive fields. Can these deficits be reversed by training? The brain is plastic and perhaps it would be possible, for example, to remold the sensory receptive fields? As a proof of principle, it has been demonstrated that sensory training with the learning of Braille can improve sensory discrimination and motor performance. Motor training to increase individuation of finger movements can also improve motor performance. These changes are mild, however, and when the training is over, the deficits return. The changes might not endure since the underlying abnormal inhibition has not been repaired. EDITORIALS