number of other regions (including the anterior cingulate, implicated in the functional connectivity studies above). After excitatory rTMS, the same double-pulse TMS now caused an increase in blood flow in the same regions, thereby demonstrating that rTMS modulates activity in a widespread cortical network. Another study evaluated changes in regional blood flow in depressed patients after 10 daily treatments of either 20-Hz or 1-Hz rTMS to the left dorsolateral prefrontal cortex (Speer et al., 2000). As predicted, 20-Hz rTMS increased blood flow in a widespread network including the L>R prefrontal cortex, the L>R cingulate gyrus, limbic cortex, thalamus and cerebellum (Figure 9). In contrast, low-frequency rTMS caused significant decreases in blood flow in right prefrontal cortex, left mesial temporal lobe, left basal ganglia and left amygdala. Importantly, patients whose mood improved after 20-Hz rTMS had worsening of their mood after 1-Hz rTMS – and for uncertain reasons, the reverse pattern was also observed in some patients. In a follow-up study (Speer et al., 2009), it was demonstrated that depressed patients with global baseline hypoperfusion had improvement after 20-Hz rTMS and worsening after 1-Hz rTMS; conversely, patients with hyperperfusion in specific cortical regions showed improvement after 1-Hz rTMS (no relationship was
