TMS coil orientation: from computational modeling to experimental evidence and analgesic considerations

Transcranial magnetic stimulation (TMS) is a widely used non-invasive brain stimulation technique whose physiological and clinical effects for pain-related indications may be critically shaped by the orientation of the stimulating coil. This scoping review aims to: 1) examine optimal coil orientation for the primary motor cortex (M1), with particular attention to the hand representation, and the dorsolateral prefrontal cortex (DLPFC), as predicted by computational modeling; 2) evaluate orientation-dependent physiological effects in healthy subjects at both M1 & DLPFC; and 3) assess evidence for coil orientation specific analgesic effects of repetitive TMS (rTMS) at M1 or DLPFC.

Following the PRISMA-ScR guidelines, seven databases (PubMed, Embase, Web of Science, Cochrane Library, ScienceDirect, DOAJ, IEEE Xplore) were searched for studies from 1992 to 2025 that compared two or more figure-of-eight coil orientations, or derived an optimal orientation, at M1 or the DLPFC. Risk of bias in the 18 studies involving human participants was assessed using ROBINS-I V2.

Twenty-four M1-related studies (8 computational, 16 experimental) and three DLPFC-related studies (2 experimental, 1 mixed experimental & computational) met the eligibility criteria. Three retrieved review articles were retained only as secondary sources. Review of the computational modeling articles indicates that while the 45° posterior-to-anterior (PA45°) orientation, referenced to the interhemispheric longitudinal fissure, provides a reliable and physiologically justified angle for M1 hand-area stimulation, optimal orientation is determined by local cortical geometry rather than a fixed angle. Computational models consistently demonstrate that the optimal angle, which induces the strongest electric field (E-field), is perpendicular to the local sulcal wall and parallel to the principal axis of the underlying cortical columns, corresponding to approximately PA45° for the M1 hand area, but differing for lower-limb representations, the pre-supplementary motor area, and the DLPFC. Human experimental findings are consistent with these predictions at M1, whereas DLPFC evidence remains sparse to specify an optimal angle. No study compared coil orientations for therapeutic analgesic outcomes.

Coil orientation has been shown to influence the induced E-field and potentially the intended analgesic benefit. However, the latter remains uninvestigated. This gap is the review's principal finding and defines a specific, testable research question.