TIDE: Tractography-Informed Dose Estimation for individualised TMS intensity

Abstract

Transcranial magnetic stimulation (TMS) is commonly dosed by setting stimulation intensity as a fixed percentage of the resting motor threshold (RMT), although a motor-derived intensity may not produce comparable neural recruitment across non-motor targets. We present TIDE (Tractography-Informed Dose Estimation), an open-source, SimNIBS-based pipeline designed to derive individualised stimulation intensities for non-motor white-matter targets. TIDE combines individual RMT measurements, finite-element electric-field modelling and diffusion MRI tractography to rescale the stimulation intensity according to the geometry and stimulation efficiency of the pathway of interest. Specifically, it computes the activating function along subject-specific streamlines and estimates the stimulator output, expressed as a percentage of maximum stimulator output, required for the target pathway to reach the activation level produced in the corticospinal tract at RMT. In an independent dataset of 19 participants, in which stimulation had been dosed conventionally as a fixed percentage of RMT, the relative difference between delivered and TIDE-estimated intensity was associated with the magnitude of TMS-induced behavioural effects at two frontal aslant tract (FAT) stimulation sites, while the delivered intensity alone was not. TIDE therefore extends conventional E-field dosing from cortical field magnitude to subject-specific pathway geometry, providing a method to move beyond the assumption of homogeneous pathway engagement while accounting for inter-individual variability in pathway-specific stimulation efficiency.