Abnormal associative plasticity of the human motor cortex in writer's cramp

Low-frequency median nerve stimulation, paired with suprathreshold transcranial magnetic stimulation (TMS) over the optimal site for activation of the abductor pollicis brevis (APB) muscle induces a long-lasting increase in the excitability of corticospinal output neurons, if median nerve stimulation is given 25 ms before TMS. Here we employed this protocol of stimulation to assess associative plasticity of the primary motor hand area in 10 patients with writer's cramp and 10 age-matched controls. Motor evoked potentials (MEPs) were recorded from right APB muscle and right first dorsal interosseus (FDI) muscle. Resting and active motor threshold, mean MEP amplitude at rest, short-latency intracortical inhibition (SICI) at an interstimulus interval of 2 ms and the duration of the cortical silent period (CSP) were assessed immediately before and after associative stimulation. In both groups, associative stimulation led to an increase in resting MEP amplitudes which was more pronounced in the right APB muscle. Compared with healthy controls, stimulation-induced facilitation of MEP amplitudes was stronger in patients with writer's cramp. In addition, only patients showed a slight decrease of resting and active motor thresholds after conditioning stimulation. In both groups, associative stimulation induced a prolongation of CSP in the APB and FDI muscles, which was significant only in the APB muscle in healthy controls. Associative stimulation had no effects on SICI in patients and healthy controls. Taken together, in patients with writer's cramp, the motor system exhibited an abnormal increase in corticospinal excitability and an attenuated reinforcement of intracortical inhibitory circuits that generate the CSP in response to associative stimulation. This altered pattern of sensorimotor plasticity may favour maladaptive plasticity during repetitive skilled hand movements and, thus, may be of relevance for the pathophysiology of writer's cramp and other task-specific dystonias.