Homeostatic-like plasticity of the primary motor hand area is impaired in focal hand dystonia

Abstract

The excitability of inhibitory circuits in patients with writer's cramp is reduced at multiple levels within the sensorimotor system, including the primary motor hand area (M1). Although this may play a major role in the pathophysiology of writer's cramp, it is still unclear what factors may cause the imbalance between inhibition and excitation to arise. One possibility is that homeostatic mechanisms that keep cortical excitability within a normal physiological range are impaired. In eight patients with writer's cramp and eight healthy age-matched controls, we combined low-frequency repetitive transcranial magnetic stimulation (rTMS) with transcranial direct current stimulation (TDCS) to probe regional homeostatic plasticity of the left M1. Confirming our previous study (Siebner et al., J Neurosci 2004; 24: 3379-85), 'facilitatory' preconditioning of the M1 with anodal TDCS enhanced the inhibitory effect of subsequent 1 Hz rTMS on corticospinal excitability. Conversely, 'inhibitory' preconditioning with cathodal TDCS reversed the after effect of 1 Hz rTMS, producing an increase in corticospinal excitability. The results were quite different in patients with writer's cramp. Following preconditioning with TDCS, 1 Hz rTMS induced no consistent changes in corticospinal excitability, indicating a loss of the normal 'homeostatic' response pattern. In addition, the normal inhibitory effect of preconditioning with cathodal TDCS was absent. The present data suggest that homeostatic mechanisms that stabilize excitability levels within a useful dynamic range are impaired in patients with writer's cramp. We propose that a faulty homeostatic response to acute increases in corticospinal excitability favours maladaptive motor plasticity. The role of homeostatic-like plasticity in the pathophysiology of task-specific dystonias warrants further study.

Enhanced Long-Term Potentiation-Like Plasticity of the Trigeminal Blink Reflex Circuit in Blepharospasm

“…The enhanced modifiability of the R2 response in patients with BEB is consistent with an increasing body of research suggesting that focal task-specific dystonias of the hand result from aberrant sensorimotor plasticity (Berardelli et al, 1998;Hallett, 1998;Quartarone et al, 2003Quartarone et al, , 2005. In monkeys, rapid, repetitive, stereotypical movements in a learning context can actively degrade the cortical representations of sensory information that guide fine hand movements (Byl et al, 1996).…”

Effects of Repetitive Transcranial Magnetic Stimulation on Dystonia: An Overview

“…Dystonia is triggered or worsened by injury that increases long-term potentiation (LTP) in the cortex that corresponds to the injured limb. From an experimental point of view, dystonia is associated with an excessive response to several plasticity-inducing protocols, e.g., rTMS (Quartarone et al, 2005). These data support the hypothesis that in dystonia there is an increased tendency to form associations between inputs and outputs, which could lead to abnormal unwanted connections and subsequent impairment of motor control.…”

Dystonia Pathophysiology: A Critical Review

“…TBS after-effect was enhanced in dystonic patients but not in their symptomatic relatives (185). Moreover, in dystonic patients, cortical responses to 1Hz rTMS is unaffected by pre-conditionning with anodal TDCS contrarily to normal controls (179,181). In dystonia, there would be an increased tendency to form associations between sensory inputs and motor inputs which may lead to de-differentiation of motor representations in accordance with the theory of synaptic homeostatis (7,186,187).…”

“…In humans, the physiological basis of LTP and LTD is limited to TMS and transcranial direct current stimulation (TDCS) of the cerebral cortex (7). Two main techiques have been used to study plasticity at the cortical level: repetitive TMS (rTMS) with variable frequencies inducing either LTP or LTD (172,178) and paired-associative stimulation (PAS) combining electrical stimulation of a peripheral nerve and cortical TMS (172,179,180). It was shown that the sensorimotor cortex (SM) exhibited an exaggerated responsiveness to rTMS responding protocols (90,(181)(182)(183)(184).…”