TMS alters multivoxel patterns in the absence of overall activity changes

Transcranial magnetic stimulation (TMS) has become one of the major tools for establishing the causal role of specific brain regions in perceptual, motor, and cognitive processes. Nevertheless, a persistent limitation of the technique is the lack of clarity regarding its precise effects on neural activity. Here, we examined the effects of TMS intensity and frequency on concurrently recorded blood-oxygen level-dependent (BOLD) signals at the site of stimulation. In two experiments, we delivered TMS to the dorsolateral prefrontal cortex in human subjects of both sexes. In Experiment 1, we delivered a series of pulses at high (100% of motor threshold) or low (50% of motor threshold) intensity, whereas in Experiment 2, we always used high intensity but delivered stimulation at four different frequencies (5, 8.33, 12.5, and 25 Hz). We found that the TMS intensity and frequency could be reliably decoded using multivariate analysis techniques even though TMS had no effect on overall BOLD activity at the site of stimulation in either experiment. These results provide important insight into the mechanisms through which TMS influences neural activity. SignificanceTranscranial magnetic stimulation (TMS) is a promising tool for the treatment of a number of neuropsychiatric disorders. However, its effectiveness is still impeded by an incomplete understanding of its neural effects. One fundamental unresolved issue is whether TMS leads to local changes in overall neural activity in the absence of a task. Here we performed two experiments where TMS was delivered inside an MRI scanner while brain activity was continuously monitored. We found converging evidence for the notion that TMS affects the pattern of local activity changes but does not lead to an overall increase in activity. These results help clarify the mechanisms of how TMS affects local neural activity.