The last few years have seen important advances in the better understanding of human cortical physiology. Functional neuroimaging and transcranial magnetic stimulation (TMS) have allowed us to address novel questions and shed different and complementary information on human brain function. In particular, TMS, a non-invasive and virtually painless tool for delivering currents in the brain, has enhanced our understanding of perceptual and motor functions in intact humans. At the same time it has also yielded data on phenomenology, mechanisms, and strategies to modulate these plastic changes in health and disease. Studies using a paired-pulse protocol (Kujirai et al. 1993) allowed detailed investigations of intracortical excitatory and inhibitory interactions in the human motor cortex. This protocol studied the effects of a TMS pulse, delivered at a subthreshold intensity to elicit a motor evoked potential (MEP), on the MEP response to an upcoming suprathreshold TMS pulse. Depending on the interval, the effect of this conditioning pulse may be inhibitory (intracortical inhibition) or excitatory (intracortical facilitation). Abnormalities in these interactions have been described in Parkinson's disease and dystonia (Ridding et al. 1995); differences with control measures have also been described as a function of motor training or learning (Liepert et al. 1998). This protocol has allowed investigators to study mechanisms of both disease and cortical reorganization, for example after amputations (Chen et al. 1998) or motor training processes.

Mechanisms underlying perceptual processes have been more difficult to study. One way to improve our understanding of these mechanisms is to identify excitatory and inhibitory interactions in brain regions involved in processing perceptual functions such as vision, tactile discrimination, or hearing. Preliminary, but so far limited, attempts have been made to examine these processes in the visual cortex. One of the obvious difficulties in performing such studies is the type of endpoint measure utilized: while intracortical inhibition and facilitation (ICI and ICF) studies in motor cortex utilize easily measurable MEP amplitudes, studies of perceptual functions must rely on human reports or the lack of them. These measures are often more variable and therefore more difficult to quantify and control. The elegant study by Oliveri et al. (2000) in this issue of The Journal of Physiology represents an important step in this direction. Using a paired-pulse protocol these authors identified excitatory and inhibitory interactions with millisecond-by-millisecond precision in a tactile perceptual process. The main finding was identification of a disruptive effect of paired pulses delivered 1 ms apart and a facilitatory effect of paired pulses delivered 5 ms apart on tactile perception. If this phenomenon is reproducible across laboratory boundaries, it may provide a useful tool to probe mechanisms underlying tactile discrimination.

A virtue of the paper by Oliveri et al. (2000) is that it opens the way for future studies which will focus on elucidating mechanisms underlying higher cognitive functions. It will be important to determine whether these interactions occur at cortical and/or subcortical sites. In the motor cortex, GABAergic and glutamatergic neurotransmission have been linked to ICI and ICF. Is it possible to identify similar neurotransmitter systems operating in this setting? If so, this tool might help to explain the mechanisms involved. It is important to address another clinically relevant question: is it possible to induce lasting changes in tactile perceptual abilities? This is likely to become an issue of interest for both basic and clinical scientists. The results presented by Oliveri et al. (2000) represent an interesting step in this direction.