Beyond inhibition: Exploiting the potential of state-dependency in cognitive and therapeutic TMS studies

Transcranial magnetic stimulation is one of a relatively small number of techniques that allow for direct intervention in neural processes in healthy human subjects and it is frequently used as a 'virtual lesion' technique to establish whether a cortical region is essential to specific cognitive processes. While these studies are typically thought of as being equivalent to disruption of or 'turning off' a stimulation site, there is potential for a greater degree of sophistication in not only elucidating temporal characteristics of cortical involvement in behavioural processes (which has been employed in numerous studies), but also interactions with factors such as cortical excitability (which is much less investigated). In relation to the later, recent studies have shown that manipulating the activational state of a brain area prior to stimulation can also result in behavioral enhancement. Here we discuss this work and describe the potential of approaches involving manipulation of excitability for extending the scope of TMS investigations of cognitive processes.