Short-interval Intracortical Inhibition Blocks Long-term Potentiation Induced by Paired Associative Stimulation

Paired associative stimulation (PAS) of the motor cortex leads to increased motor evoked potential (MEP) amplitudes in the stimulated hand muscles. We hypothesized that evoking GABA(A) receptor-mediated short-interval intracortical inhibition (SICI) simultaneously with excitatory PAS would depress long-term potentiation plasticity in motor cortex. Four different PAS paradigms were tested, standard PAS (PAS25) and three conditioned PAS protocols (CS2-PAS25, CS2-PAS25adj, and CS10-PAS25adj). A subthreshold conditioning stimulus 2 ms (CS2) or 10 ms (CS10) before the test stimuli was added to the conditioned PAS protocols. Since CS2 has inhibitory and CS10 has facilitatory effect on cortical excitability, in the CS2-PAS25adj and CS10-PAS25adj protocols, TS intensity was adjusted to produce a 1-mV MEP in the presence of CS2 or CS10 to control for the degree of corticospinal excitation. As expected, MEP amplitudes after PAS25 were higher compared with that at baseline, but importantly, MEP amplitudes did not change after PAS was induced in the presence of SICI in either the CS2-PAS25 or CS2-PAS25adj condition. Furthermore, the CS10-PAS25adj protocol showed significantly increased MEP amplitude at 60 min after PAS compared with baseline. These results show that SICI blocked the induction of long-term potentiation-like plasticity in the motor cortex, indicating that GABAergic circuits play an important role in the regulation of cortical plasticity. The study demonstrates a noninvasive and nonpharmacological way to achieve focal modulation of plasticity.