The virtual lesion approach to transcranial magnetic stimulation: studying the brain-behavioral relationships in experimental pain

Transcranial magnetic stimulation (TMS) can be used to create a temporary virtual lesion (VL) of a target cortical area, disrupting its function and associated behavior. Transcranial magnetic stimulation can therefore test the functional role of specific brain areas. This scoping review aims at investigating the current literature of the online TMS-evoked VL approach to studying brain-behavioral relationships during experimental pain in healthy subjects. Ovid-Medline, Embase, and Web of Science electronic databases were searched. Included studies tested different TMS-based VLs of various pain brain areas during continuous experimental pain or when time-locked to a noxious stimulus. Outcome measures assessed different pain measurements. Initial screening resulted in a total of 403 studies, of which 17 studies were included in the review. The VLs were directed to the prefrontal, primary and secondary somatosensory, primary motor, and parietal cortices through single/double/triple/sequence of five-TMS pulses or through repeated TMS during mechanical, electrical contact, radiant heat, or capsaicin-evoked noxious stimulation. Despite a wide variability among the VL protocols, outcome measures, and study designs, a behavioral VL effect (decrease or increase in pain responses) was achieved in the majority of the studies. However, such findings on the relationships between the modified brain activity and the manifested pain characteristics were often mixed. To conclude, TMS-elicited VLs during experimental pain empower our understanding of brain-behavior relationships at specific time points during pain processing. The mixed findings of these relationships call for an obligatory standard of all pain-related TMS protocols for clearly determining the magnitude and direction of TMS-induced behavioral effects.