Network-specific metabolic and haemodynamic effects elicited by non-invasive brain stimulation

Repetitive transcranial magnetic stimulation (TMS), when applied to the dorsolateral prefrontal cortex (dlPFC), treats depression. Therapeutic effects are hypothesized to arise from propagation of local dlPFC stimulation effects across distributed networks; however, the mechanisms of this remain unresolved. dlPFC contains representations of different networks. As such, dlPFC TMS may exert different effects depending on the network being stimulated. Here, to test this, we applied high-frequency TMS to two nearby dlPFC targets functionally embedded in distinct anti-correlated networks-the default and salience networks- in the same individuals in separate sessions. Local and distributed TMS effects were measured with combined ¹⁸fluorodeoxyglucose positron emission tomography and functional magnetic resonance imaging. Identical TMS patterns caused opposing effects on local glucose metabolism: metabolism increased at the salience target following salience TMS but decreased at the default target following default TMS. At the distributed level, both conditions increased functional connectivity between the default and salience networks, with this effect being dramatically larger following default TMS. Metabolic and haemodynamic effects were also linked: across subjects, the magnitude of local metabolic changes correlated with the degree of functional connectivity changes. These results suggest that TMS effects upon dlPFC are network specific. They also invoke putative antidepressant mechanisms of TMS: network de-coupling.