Homeostatic plasticity of the motor cortex is impaired in focal dystonia

Background: In patient with writer's cramp, the excitability of inhibitory circuits has been shown to be reduced at multiple levels within the sensorimotor system, including the primary motor hand area (M1). Though deficient sensorimotor inhibition is thought to play a major role in the pathophysiology of writer's cramp, it is unclear which mechanisms lead to an imbalance in regional excitability. One possibility is that homeostatic mechanisms which keep cortical excitability levels within a normal physiological range are impaired in focal hand dystonia.

Methods: In eight patients with writer's cramp and eight healthy age-matched controls, we combined low-frequency repetitive transcranial magnetic stimulation (rTMS) with transcranial DC stimulation (TDCS) to probe regional homeostatic plasticity of the left M1.

Results: Confirming our previous study (Siebner et al., J Neurosci 2004; 24:3379–3385), „facilitatory“ pre-conditioning of the M1 with anodal TDCS enhanced the inhibitory effect of subsequent 1Hz rTMS on corticospinal excitability. After „inhibitory“ pre-conditioning with cathodal TDCS the after effect of 1Hz-rTMS was reversed producing an increase in corticospinal excitability. The response to TDCS pre-conditioning and subsequent rTMS was markedly altered in patients with writer's cramp. Anodal TDCS increased corticospinal excitability, whereas pre-conditionong with cathodal TDCS produced no after-effect on corticospinal excitability. Following TDCS pre-conditioning, 1Hz-rTMS produced no consistent changes in corticospinal excitability, indicating a loss of the normal „homeostatic“ response pattern. Importantly, 1Hz-rTMS failed to reverse the increase in corticospinal excitability produced by the preceding anodal TDCS.

Conclusion: The present data corrobates the notion that corticospinal excitability is abnormally modifiable in writer's cramp. The critical new finding is that homeostatic mechanisms which stabilize excitability levels within a useful dynamic range are impaired in writer's cramp. A faulty homeostatic response to acute increases in cortical excitability may favour maladaptive plasticity resulting in a progressive shift in cortical excitability towards abnormal facilitation and loss of inhibition. Deficient homeostatic plasticity may thus play a major role in the pathophysiology of writer's cramp and other task-specific dystonias.