Mechanisms of action underlying the effect of repetitive transcranial magnetic stimulation on mood: behavioral and brain imaging studies.

In a set of experiments, we applied 10-Hz repetitive transcranial magnetic stimulation (rTMS) over the left mid-dorsolateral frontal cortex (MDLFC) to investigate rTMS-induced changes in affective state and neural activity in healthy volunteers. In Experiment 1, we combined 10-Hz rTMS with a speech task to examine rTMS-induced changes in paralinguistic aspects of speech production, an affect-relevant behavior strongly linked to the ACC. In Experiment 2, we combined 10-Hz rTMS with positron emission tomography (PET) and used partial least squares (PLS) to identify a pattern of brain regions whose connectivity with the site of stimulation varied as a function of rTMS. The results of Experiment 1 revealed that following stimulation of the left MDLFC, subjects reported having less positive affect and vitality and displayed more monotonous speech. In Experiment 2, results revealed that 10-Hz rTMS influenced the covariation between blood flow at the site of stimulation (ie the left MDLFC) and blood flow in a number of affect-relevant brain regions including the perigenual anterior cingulate gyrus, insula, thalamus, parahippocampal gyrus, and caudate nucleus. Taken together, our results suggest that changes in affect and affect-relevant behaviour following 10-Hz rTMS applied over the left MDLFC may be related to changes in neural activity in brain regions widely implicated in affective states, including a frontocingulate circuit.