Functional connectivity- and E-field-optimized TMS targeting: method development and concurrent TMS-fMRI validation

Effectiveness of personalized, functional connectivity (FC)-guided TMS might further profit from optimizing coil position and orientation based on electric field (E-field) simulations. However, existing optimization routines (as implemented in, e.g., SimNIBS) typically only consider the E-field in a small cortical patch surrounding a single target coordinate, thus ignoring the whole-brain topography of both the subject-specific FC map and E-field. To increase target specificity of FC-guided TMS, we developed an optimization approach that takes into account the available spatial information. More specifically, within our approach, the optimal combination of coil position and orientation simultaneously maximizes (i) overlap between E-field and FC target cluster and (ii) E-field strength in the target cluster, while (iii) minimizing overlap with non-target areas across the whole brain. In ongoing work, we test the validity of this approach by applying TMS at the optimized position and orientation during a concurrent fMRI measurement (TMS-fMRI). We show that our optimization approach results in a very good overlap between subject-specific FC target clusters and simulated E-fields, with minimal off-target coverage. Moreover, concurrent TMS-fMRI shows specific TMS-induced BOLD modulations in both the directly stimulated, superficial target area as well as functionally connected cortical and subcortical regions. We will continue validating this approach and hope that it will further increase the specificity and effectiveness of personalized TMS in, e.g., psychiatry. Research Category and Technology and Methods Basic Research: 10. Transcranial Magnetic Stimulation (TMS) Keywords: Functional connectivity, Electric field simulation, Personalized, Concurrent TMS-fMRI