Moving towards precision TMS? Evaluating individual differences and reproducibility of personalized stimulation targets in UK Biobank

Abstract:

Objective Personalized transcranial magnetic stimulation (TMS) targeting, guided by functional connectivity (FC), shows potential in treating depression. The present study aims to map individual FC peak location using UK Biobank, to evaluate individual differences and reproducibility of FC-based targets. Methods We analyzed UK Biobank resting-state fMRI (rfMRI) of 35,423 participants, identifying individual FC peak locations on the dorsolateral prefrontal cortex (DLPFC) that functionally connected to the subcallosal cingulate, amygdala, and ventromedial prefrontal cortex, respectively. Euclidean distance between each participant’s individual peak and group-average peak was calculated. With follow-up rfMRI of 1341 participants, within-subject FC peak location changes were calculated. We also compared common TMS targets and random locations for their median distance to individual peaks in a permutation test. Results Seed-based FC analyses revealed large differences in the individual FC peak location on DLPFC: the mean distance from the individual peaks to group-average peak ranged from 14.24 to 29.92mm; 70% to 94% of participants were >10mm away from the group-average peak and potentially located outside of the TMS effective area with common TMS coils. Similar variability was observed in within-subject peak locations across two fMRI assessments. Common TMS targets and the group-average FC peak showed no significant difference in median distances to individual FC peaks when compared to random locations. Conclusions FC peak location shows wide inter- and intra-individual variability. We emphasize a role for individualized TMS neuronavigation targeting but emphasize the need for more reliable biomarker studies.