The neural mechanisms by which rTMS modulates depression are unknown, but two (non-exclusive) hypotheses are that 1) rTMS directly modulates activity (e.g. via synaptic plasticity mechanisms) in the frontocingulate network that is associated with depression, or 2) rTMS may facilitate monoaminergic transmission, with a likely diverse impact on the neurochemical milieu (Paus & Barrett, 2004). Indeed, several studies have suggested that prefrontal rTMS affects serotonin synthesis and dopamine release in a number of other cortical regions (Pogarell et al., 2006; Sibon et al., 2007; Cho & Strafella, 2009). To explore how rTMS of frontal cortex affects cortical activity in other regions, Paus et al. (2001) conducted a study combining rTMS of dorsolateral prefrontal cortex with PET. Intriguingly, the authors demonstrated that an initial test stimulus (double-pulse TMS) caused decreased blood flow in both the area being stimulated and in a 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
