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Paired associative stimulation (PAS) refers to a paradigm consisting of slow-rate repetitive low-frequency median nerve stimulation combined with transcranial magnetic stimulation (TMS) over the contralateral motor cortex. This protocol has been shown to induce plastic changes of excitability in the human motor cortex. Its principles of design were shaped after associative long-term potentiation (LTP) in experimental animals, a cellular mechanism likely to be relevant for learning and memory. PAS-induced changes of cortical excitability share a number of physiological properties with LTP. Of particular importance is the fact that the sign of PAS-induced changes of the size of amplitudes of the motor evoked potentials (MEPs) depends on the exact interval between the afferent and the magnetic pulse during the intervention. A number of observations suggest that PAS-induced excitability changes may have functional significance. PAS-induced plasticity may contribute to elucidating the pathogenesis of neurological disorders where neuroplasticity is thought to have a pathogenetic role. Finally, PAS-induced plasticity may itself have therapeutic potential.

The role of attention in generating motor memories remains controversial principally because it is difficult to separate the effects of attention from changes in kinematics of motor performance. We attempted to disentangle attention from performance effects by varying attention while plasticity was induced in human primary motor cortex by external stimulation in the absence of voluntary movement. A paired associative stimulation (PAS) protocol was employed consisting of repetitive application of single afferent electric stimuli, delivered to the right median nerve, paired with single-pulse transcranial magnetic stimulation (TMS) over the optimal site for activation of the right abductor pollicis brevis muscle (APB) to generate near-synchronous events in the left primary motor cortex. In experiment 1, the spatial location of attention was varied. PAS failed to induce plasticity when the subject's attention was directed to their left hand, away from the right target hand the cortical representation of which was being stimulated by PAS. In experiment 2, the grade of attention to the target hand was manipulated. PAS-induced plasticity was maximal when the subject viewed their target hand, and its magnitude was slightly reduced when the subject could only feel their hand. Conversely, plasticity was completely blocked when the subject's attention was diverted from the target hand by a competing cognitive task. A similar modulation by attention was observed for PAS-induced changes in the duration of the silent period evoked by TMS in voluntarily contracted muscle. Associative plasticity in the human motor cortex depends decisively on attention. [ABSTRACT FROM AUTHOR]