Proximity to an SGC-DLPFC Individualized Functional Target and Electric-Field Modeling Do Not Predict Clinical Outcomes of rTMS for Treatment-Resistant Depression.

Abstract

Targeting methods for repetitive transcranial magnetic stimulation (rTMS) in patients with depression now include individual functional magnetic resonance imaging (fMRI) scans to target specific functional connectivity (FC) patterns. Potential biomarkers of rTMS response include target FC with the subgenual anterior cingulate cortex (SGC) or the causal depression circuit (CDC), each of which may be candidates for individualized functional targets (iFTs). We retrospectively assessed the relationship of these two approaches to outcomes in secondary analyses of two large rTMS clinical trials. 501 subjects with moderate to severe depression underwent 4-6 weeks of daily rTMS to the left dorsolateral prefrontal cortex (DLPFC), targeted using neuronavigation to an optimized DLPFC-SGC-FC group-based functional target. Baseline resting-state scans were used to retrospectively compute iFTs using either SGC-DLPFC or CDC-DLPFC FC. Proximity (Euclidean distance) of the stimulated target to iFTs were correlated with outcomes. Electric field magnitude at iFTs was computed to capture non-linear stimulation propagation. Most iFTs were within 2cm of their group-target. Proximity to either an SGC- or CDC-iFT was not associated with better outcomes. Sensitivity analyses accounting for treatment target FC, methodology, data quality, or treatment parameters did not change results. Electric field-based measures were highly similar to Euclidean distance and likewise showed no association with outcomes. Under the specific fMRI acquisition parameters used, proximity to optimized DLPFC-SGC-iFTs was not associated with better outcomes in patients receiving neuronavigated rTMS to an optimized DLPFC-SGC group-target. Prospective randomized clinical trials definitively assessing the clinical utility of iFTs are warranted. .