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

TLDR

Motor‑cortical plasticity models emphasize the joint role of somatosensory afferents and intrinsic motor circuits. The study tested whether paired median‑nerve and TMS stimulation can induce lasting excitability changes in human motor cortex. The protocol paired low‑frequency median‑nerve stimulation with TMS over the abductor pollicis brevis motor hotspot. Paired stimulation increased resting MEP amplitudes and silent‑period duration, localized to the motor cortex, depended on precise timing, emerged within 30 min, persisted 30–60 min, and was reversible, indicating associative LTP‑like plasticity.

Abstract

Current models of motor cortical plasticity, developed in studies on experimental animals, emphasize the importance of the conjoint activity of somatosensory afferents and intrinsic motor cortical circuits. The hypothesis that an enduring change in excitability in the cortical output circuitry can be induced in the human motor cortex by a paired-stimulation protocol was tested. Low-frequency median nerve stimulation was paired with transcranial magnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB). This protocol induced an increase in the amplitudes of the motor evoked potentials (MEPs) in the resting APB as well as a prolongation of the silent period measured in the precontracted APB following TMS; amplitudes of MEPs measured in voluntary contraction remained unchanged. Experiments testing the excitability of spinal motoneurons using F-wave studies and electrical stimulation of the brainstem suggested that the site of the plastic changes was within the motor cortex. The increases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation in that they were present when events elicited by afferent and magnetic stimulation were synchronous at the level of the motor cortex. Plasticity induced by paired stimulation evolved rapidly (within 30 min), was persistent (minimum 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, leads us to propose that the induced plasticity may represent a signature of associative long-term potentiation of cortical synapses or closely related neuronal mechanisms in the human cortex.