GABAergic mechanisms involved in the prepulse inhibition of auditory evoked cortical responses in humans

Despite their essential roles in signal processing in the brain, the functions of interneurons currently remain unclear in humans. We recently developed a method using the prepulse inhibition of sensory evoked cortical responses for functional measurements of interneurons. When a sensory feature is abruptly changed in a continuous sensory stimulus, change-related cortical responses are recorded using MEG. By inserting a weak change stimulus (prepulse) before the test change stimulus, it is possible to observe the inhibition of the test response. By manipulating the prepulse–test interval (PTI), several peaks appear in inhibition, suggesting the existence of temporally distinct mechanisms. We herein attempted to separate these components through the oral administration of diazepam and baclofen. The test stimulus and prepulse were an abrupt increase in sound pressure in a continuous click train of 10 and 5 dB, respectively. The results obtained showed that the inhibition at PTIs of 10 and 20 ms was significantly greater with diazepam than with the placebo administration, suggesting increased GABA(A)-mediated inhibition. Baclofen decreased inhibition at PTIs of 40 and 50 ms, which may have been due to the activation of GABA(B) autoreceptors. Therefore, the present study separated at least two inhibitory mechanisms pharmacologically.