Such combined-modality studies permit analysis of precisely how different regions interact. Because the TMS pulse produces a change in brain activity at a particular place and time, various techniques that assess how that change is propagated through the brain can be used to assess metrics of effective connectivity. For example, in a recent study, TMS was applied to the left motor hand region while brain activity was imaged with PET (Laird et al., 2008). Structural equation modeling was then applied to the PET data to evaluate the connectivity, focusing on regions known to be activated during TMS to motor cortex. Since TMS was being applied to a single (known) location at a specific time point, the sequence and direction of interactions with other cortical regions could be precisely delineated, permitting the construction of a detailed activity-path model. Following TMS of left motor cortex, activity initially propagated to five regions: the supplementary motor area, the cingulate gyrus, the left ventral nucleus of the thalamus, the right secondary somatosensory cortex, and the right cerebellum. From these initial points, activity then propagated through a number of additional regions (Figure 7).
