Focal hand dystonia: Using brain stimulation to probe network interactions and brain plasticity

Focal hand dystonias such as writer’s cramp and musician’s cramp are intriguing disorders, and their pathophysiology remains incompletely understood. Both the motor and sensory systems are abnormal in dystonia. In the motor system, dystonia is characterized by loss of inhibition at multiple levels in the central nervous system. In the motor cortex, both inhibitory cortical circuits and surround inhibition are reduced in dystonia. There is also involvement of the sensory system. Patients with focal hand dystonia exhibit abnormal somatotopy with overlapping digit representations in primary somatosensory cortex, together with diminished temporal and spatial tactile acuity. Recent studies indicate that altered integration of somatosensory information into the motor plan within the sensorimotor circuit is a key pathophysiological feature of dystonia. Patients with focal hand dystonia have disturbances of perceptual body representations and reduced connectivity between parietal and premotor regions that control writing. It is generally considered that abnormalities in the basal ganglia and the cerebellum lead to changes in the primary motor and sensory cortices in dystonia. Excessive plasticity and abnormal regulation of plasticity are considered major pathophysiological features of dystonia. Several studies showed that dystonia is associated with exaggerated long-term potentiation (LTP)-like cortical plasticity. consistent with the hypothesis that dystonia is a disorder of synaptic “scaling. ” Exaggerated LTP-like plasticity may lead to an excessive tendency to form associations between sensory inputs and motor outputs (abnormal potentiation) and failure to weaken already existing associations (deficient depotentiation). Deficient homeostatic control of plasticity might trigger maladaptive reorganization and produce dystonic symptoms. Recent advances in noninvasive brain stimulation (NIBS) techniques provide a powerful tool to understand the complex interactions both within various circuits of the primary motor cortex (M1) and between different connected sensory-motor areas, and to induce brain plasticity in humans. Transcranial magnetic stimulation (TMS) is a widely used technique that allows noninvasive examination of different inhibitory and excitatory circuits at the systems level in the human brain, and has the potential to be used as a diagnostic and prognostic tool. Interactions between two nodes of a neural circuit in the human sensory-motor system can be studied using two coils in a paired-pulse TMS protocol. In this conditioning-test paradigm, a conditioning stimulus is delivered to a non-motor area to examine its effects on a subsequent test stimulus to motor cortex. This approach provides information on the excitability of cortical projections to M1 with millisecond resolution, and how inputs from other areas to M1 are modulated by different task-demands, disease, or injury. In addition, several TMS protocols can be used to induce and measure cortical plasticity and they have potential therapeutic utilities in movement disorders. Paired associative stimulation (PAS), modeled after LTP induction protocols in animal studies, induces LTPlike plasticity by repeated pairing of electrical stimulus to the median nerve with TMS to M1, with the median nerve stimulation preceding TMS by approximately 25 ms such that the two inputs are timed to arrive at the M1 at roughly the same time. It acts through sensory-motor communications and intracortical circuits of M1, and produces heterosynaptic (involves two different synapses), spike-timing– dependent plasticity. In the current issue of Movement Disorders, two studies used these relatively new NIBS methods to examine the pathophysiology of focal hand dystonia. Pirio Richardson et al. used paired-pulse TMS to examine the interactions between dorsal premotor cortex (PMd) and ipsilateral M1 in patients with writer’s -----------------------------------------------------------*Correspondence to: Dr. Robert Chen, McLaughlin Pavilion, 7th Floor, Room 411, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8, E-mail: robert.chen@uhn.ca