Long-term potentiation (LTP) and long-term depression (LTD) are regulated by homeostatic control mechanisms to maintain synaptic strength in a physiological range. Although homeostatic metaplasticity has been demonstrated in the human motor cortex, little is known to which extent it operates in other cortical areas and how it links to behavior. Here we tested homeostatic interactions between two stimulation protocols—paired associative stimulation (PAS) followed by peripheral high-frequency stimulation (pHFS)—on excitability in the human somatosensory cortex and tactile spatial discrimination threshold. PAS employed repeated pairs of electrical stimulation of the right median nerve followed by focal transcranial magnetic stimulation of the left somatosensory cortex at an interstimulus interval of the individual N20 latency minus 15 msec or N20 minus 2.5 msec to induce LTD- or LTP-like plasticity, respectively [Wolters, A., Schmidt, A., Schramm, A., Zeller, D., Naumann, M., Kunesch, E., et al. Timing-dependent plasticity in human primary somatosensory cortex. Journal of Physiology, 565, 1039–1052, 2005]. pHFS always consisted of 20-Hz trains of electrical stimulation of the right median nerve. Excitability in the somatosensory cortex was assessed by median nerve somatosensory evoked cortical potential amplitudes. Tactile spatial discrimination was tested by the grating orientation task. PAS had no significant effect on excitability in the somatosensory cortex or on tactile discrimination. However, the direction of effects induced by subsequent pHFS varied with the preconditioning PAS protocol: After PASN20-15, excitability tended to increase and tactile spatial discrimination threshold decreased. After PASN20-2.5, excitability decreased and discrimination threshold tended to increase. These interactions demonstrate that homeostatic metaplasticity operates in the human somatosensory cortex, controlling both cortical excitability and somatosensory skill.

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