Sensory representation abnormalities that parallel focal hand dystonia in a primate model

In our hypothesis of focal dystonia, attended repetitive behaviors generate aberrant sensory representations. Those aberrant representations interfere with motor control. Abnormal motor control strengthens sensory abnormalities. The positive feedback loop reinforces the dystonic condition. Previous studies of primates with focal hand dystonia have demonstrated multi-digit or hairy-glabrous responses at single sites in area 3b, receptive fields that average ten times larger than normal, and high receptive field overlap as a function of horizontal distance. In this study, we strengthen and elaborate these findings. One animal was implanted with an array of microelectrodes that spanned the border between the face and digits. After the animal developed hand dystonia, responses in the initial hand representation increasingly responded to low threshold stimulation of the face in a columnar substitution. The hand-face border that is normally sharp became patchy and smeared over 1 mm of cortex within 6 weeks. Two more trained animals developed a focal hand dystonia variable in severity across the hand. Receptive field size, presence of multi-digit or hairy-glabrous receptive fields, and columnar overlap covaried with the animal's ability to use specific digits. A fourth animal performed the same behaviors without developing dystonia. Many of its physiological measures were similar to the dystonic animals, but receptive field overlap functions were minimally abnormal, and no sites shared response properties that are normally segregated such as hairy-glabrous combined fields, or multi-digit fields. Thalamic mapping demonstrated proportionate levels of abnormality in thalamic representations as were found in cortical representations.     

A nose that looks like a hand and acts like an eye: the unusual mechanosensory system of the star-nosed mole

The star-nosed mole (Condylura cristata) has a snout surrounded by 22 fleshy and mobile appendages. This unusual structure is not an olfactory organ, as might be assumed from its location, nor is it used to manipulate objects as might be guessed from its appearance. Rather, the star is devoted to the sense of touch, and for this purpose the appendages are covered with thousands of small mechanoreceptive Eimer's organs. Recent behavioral studies find that the star acts much like a tactile eye, having a small behavioral focus, or “fovea” at the center – used for detailed explorations of objects of interest. The peripheral and central nervous systems of the mole reflect these behavioral specializations, such that the small behavioral focus on the nose is more densely innervated in the periphery, and has a greatly enlarged representation in the somatosensory cortex. This somatosensory representation of the tactile fovea is not correlated with anatomical parameters (innervation density) as found in other species, but rather is highly correlated with patterns of behavior. The many surprising parallels between the somatosensory system of the mole, and the visual systems of other mammals, suggest a convergent and perhaps common organization for highly developed sensory systems. Accepted: 31 May 1999     

Progressive changes in cutaneous trigger zones for sensation referred to a phantom hand: a case report and review with implications for cortical reorganization

The dominant model of cortical plasticity induced by peripheral denervation suggests that a physiologically-reorganized cortical area can acquire new perceptual meaning, including a change in the peripheral referral of sensation. An alternative view is that such an area may retain its former perceptual significance, even though it becomes responsive to new peripheral inputs. To examine evidence related to this issue, a clinical case is presented documenting the time course of changes in phantom limb sensation in a patient with accidental amputation of a hand. About 24 h after injury, a vivid phantom hand was present; tactile stimulation revealed cutaneous trigger zones on the arm, stimulation of which elicited sensation referred to specific fingers of the phantom. While the phantom hand percept remained fairly stable over time, the trigger zones expanded progressively in size during the next 1-8 weeks but had contracted and changed location considerably about one year later. At all times studied, the trigger zones were topographically related to specific fingers and other parts of the phantom hand. The implications of these and other recent clinical findings for cortical reorganization are discussed, and the following tentative conclusions are drawn. (1) A phantom percept is mediated by central neural networks which remain functionally intact after amputation. (2) Cutaneous trigger zones mapped in humans correspond to novel receptive fields of cortical neurons mapped in animals following peripheral denervation. (3) Cortical reorganization induced by denervation does not produce a major change in perceptual meaning or peripheral reference. In the present case, stimulation of new trigger zones (receptive fields) on the patient's arm presumably activated a reorganized cortical hand area but evoked sensation still referred to the (now missing) hand. Hence, physiological cortical remapping is not necessarily accompanied by functional respecification.     

Search for a founder mutation in idiopathic focal dystonia from Northern Germany.

Both the discovery of the DYT1 gene on chromosome 9q34 in autosomal dominant early-onset torsion dystonia and the detection of linkage for one form of adult-onset focal dystonia to chromosome 18p (DYT7) in a family from northern Germany provide the opportunity to further investigate genetic factors in the focal dystonias. Additionally, reports of linkage disequilibrium between several chromosome 18 markers and focal dystonia, both in sporadic patients from northern Germany and in members of affected families from central Europe suggest the existence of a founder mutation underlying focal dystonia in this population. To evaluate the role of these loci in focal dystonia, we tested 85 patients from northern Germany who had primary focal dystonia, both for the GAG deletion in the DYT1 gene on chromosome 9q34 and for linkage disequilibrium at the chromosome 18p markers D18S1105, D18S1098, D18S481, and D18S54. None of these patients had the GAG deletion in the DYT1 gene. Furthermore, Hardy-Weinberg analysis of markers on 18p in our patient population and in 85 control subjects from the same region did not support linkage disequilibrium. Taken together, these results suggest that most cases of focal dystonia in patients of northern German or central European origin are due neither to the GAG deletion in DYT1 nor to a proposed founder mutation on chromosome 18p but must be caused by other genetic or environmental factors.