Recent functional imaging studies demonstrated that both the left and right supramarginal gyri (SMG) are activated when healthy right-handed subjects make phonological word decisions. However, lesion studies typically report difficulties with phonological processing after left rather than right hemisphere damage. Here, we used a unique dual-site transcranial magnetic stimulation (TMS) approach to test whether the SMG in the right hemisphere contributes to modality-independent (i.e., auditory and visual) phonological decisions. To test task-specificity, we compared the effect of real or sham TMS during phonological, semantic, and perceptual decisions. To test laterality and anatomical specificity, we compared the effect of TMS over the left, right, or bilateral SMG and angular gyri. The accuracy and reaction times of phonological decisions were selectively disrupted relative to semantic and perceptual decisions when real TMS was applied over the left, right, or bilateral SMG. These effects were not observed for TMS over the angular gyri. A follow-up experiment indicated that the threshold-intensity for inducing a disruptive effect on phonological decisions was identical for unilateral TMS over the right or left SMG. Taken together, these findings provide converging evidence that the right SMG contributes to accurate and efficient phonological decisions in the healthy brain, with no evidence that the left and right SMG can compensate for one another during TMS. Our findings motivate detailed studies of phonological processing in patients with acute or long-term damage of the right SMG.M any previous functional imaging studies have shown that the left and right supramarginal gyri (SMG) are activated when right-handed participants make decisions about the sounds of words (i.e., their phonology) compared with decisions about their meanings (i.e., their semantics) (1-4). However, the functional significance of right SMG activation is unclear because lesion studies have reported phonological difficulties following left rather than right temporo-parietal lesions (5-8). Consequently, anatomical models of phonological processing have included left but not right parietal cortex (9, 10). The present study was designed to address the discrepancy between functional imaging and lesion studies. More specifically, we examined how "online" transcranial magnetic stimulation (i.e., TMS during a task) over the left and right SMG influences phonological word processing in healthy subjects (Fig. 1). We used the neurodisruptive effect of TMS to distinguish between three alternative hypotheses to explain right SMG activation with phonological processing.Hypothesis 1 is that right SMG only contributes to the speed but not the accuracy of phonological decisions. Consequently, right SMG lesions have a subtle effect on phonological processing that might be missed unless reaction times were measured. In this case, we expect a selective effect of right SMG TMS on reaction times in the healthy brain without affecting error rates.Hypothesis 2 i...

Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures or neuronal activity patterns for a given brain function. It is nowadays feasible to combine NTBS, either consecutively or concurrently, with a variety of neuroimaging and electrophysiological techniques. Here we discuss what kind of information can be gained from combined approaches, which often are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both "online" NTBS effects immediately following the stimulation and "offline" NTBS effects outlasting plasticity-inducing NTBS protocols can be assessed. Finally, both strategies can be combined to close the loop between measuring and modulating brain activity by means of closed-loop brain state-dependent NTBS. In this paper, we will provide a conceptual framework, emphasizing principal strategies and highlighting promising future directions to exploit the benefits of combining NTBS with neuroimaging or electrophysiology.

Transcranial magnetic stimulation (TMS) uses a magnetic field to "carry" a short lasting electrical current pulse into the brain where it stimulates neurones, particularly in superficial regions of cerebral cortex. TMS can interfere with cognitive functions in two ways. A high intensity TMS pulse causes a synchronised high frequency burst of discharge in a relatively large population of neurones that is terminated by a long lasting GABAergic inhibition. The combination of artificial synchronisation of activity followed by depression effectively disrupts perceptual, motor and cognitive processes in the human brain. This transient neurodisruption has been termed a "virtual lesion". Smaller intensities of stimulation produce less activity; in such cases, cognitive operations can probably continue but are disrupted because of the added noisy input from the TNS pulse.It is usually argued that if a TMS pulse affects performance, then the area stimulated must provide an essential contribution to behaviour being studied. However, there is one exception to this: the pulse could be applied to an area that is not involved in the task but which has projections to the critical site. Activation of outputs from the site of stimulation could potentially disrupt processing at the distant site, interfering with behaviour without having any involvement in the task.A final important feature of the response to TMS is "context dependency", which indicates that the response depends on how excitable the cortex is at the time the stimulus is applied: if many neurones are close to firing threshold then the more of them are recruited by the pulse than at rest. Many studies have noted this context-dependent modulation. However, it is often assumed that the excitability of an area has a simple relationship to activity in that area. We argue that this is not necessarily the case. Awareness of the problem may help resolve some apparent anomalies in the literature.