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

Abstract

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 hairyglabrous 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 micro-electrodes 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 one millimeter of cortex within six 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 was found in cortical representations.

Experience-Dependent Plasticity in S1 Caused by Noncoincident Inputs

“…The behavior was constructed to test the range of relative input timings that can cause this form of plasticity. The range of time constants that cause reorganization has implications for reorganization in the human condition, for manual tasks such as typing, video games, and playing music, and may have importance in the generation of the pathological condition focal dystonia (Blake et al 2002a). Cortical implants were used in the experimental design to document the emergent plasticity in spiking responses across daily training sessions (deCharms et al 1999).…”

High-Field (9.4T) Magnetic Resonance Imaging in Squirrel Monkey

“…1987;Sur et al, 1984), visual (Livingstone, 1996), auditory (Cheung et al, 2001), and vestibular Guldin et al, 1992) cortices. This species has also been used extensively as a model for studies of cortical plasticity Frost et al, 2003;Nudo et al, 2003;Churchill et al, 2001;Xerri et al, 1996;Merzenich et al, 1993;Garraghty & Kaas, 1991), basal ganglia (Flaherty and Graybiel, 1991;1994;, and disease (e.g., dystonia and Parkinson's disease: Blake et al, 2002;Rupniak et al, 1992;Boyce et al, 1990).…”

Animal models of focal dystonia

“…Byl and colleagues [95][96][97]115,116 required owl monkeys to perform repetitive hand movements to receive rewards. Before beginning the task and again after the monkeys developed dystonic hand movements, the investigators measured area 3b receptive fields for the hand.…”

“…89 Associated with the disordered somatosensory cortex organization, individuals with writer's cramp exhibit deficits in somatosensory perception similar to those occurring with torticollis. [92][93][94] Based on their animal model, Byl, Merzenich, and colleagues [95][96][97][98][99][100][101][102] propose the "sensorimotor learning" hypothesis of focal hand dystonia. This hypothesis emerges from the observation that somatosensory representations in cortex are plastic and can be modified by Hebb-like processes.…”

“…Before beginning the task and again after the monkeys developed dystonic hand movements, the investigators measured area 3b receptive fields for the hand. In one task, 96,97,115 two monkeys were required to hold on to a hand piece molded to fit the hand. While the monkey gripped the hand piece, it opened and closed by 6.4 mm one to nine times.…”