Induction of plasticity in the human motor cortex by paired associative stimulation

Current models of motor cortical plasticity, developed in studies on experi mental animals, emphasize the importance of the conjoint activity of somato sensory afferents and intrinsic motor cortical circuits, The hypothesis tha t an enduring change in excitability in the cortical output circuitry can b e induced in the human motor cortex by a paired-stimulation protocol was te sted, Low-frequency median nerve stimulation was paired with transcranial m agnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB), This protocol induced an increase i n the amplitudes of the motor evoked potentials (MEPs) in the resting APE a s well as a prolongation of the silent period measured in the precontracted APE following TMS; amplitudes of MEPs measured in voluntary contraction re mained unchanged. Experiments testing the excitability of spinal motoneuron s using F-wave studies and electrical stimulation of the brainstem suggeste d that the site of the plastic changes was within the motor cortex, The inc reases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation i n that they were present when events elicited by afferent and magnetic stim ulation were synchronous at the level of the motor cortex. Plasticity induc ed by paired stimulation evolved rapidly (within 30 min), was persistent (m inimum duration 30-60 min) yet reversible, and was topographically specific , This combination of features and the similarity to properties of induced enduring changes in synaptic efficacy, as elucidated in animal studies, lea ds us to propose that the induced plasticity may represent a signature of a ssociative long-term potentiation of cortical synapses or closely related n euronal mechanisms in the human cortex.