Mapping Inter-individual Functional Connectivity Variability in TMS Targets for Major Depressive Disorder

Area of Science:

• Neuroscience
• Medical Imaging
• Psychiatry

Background:

• Transcranial Magnetic Stimulation (TMS) is an emerging treatment for major depressive disorder (MDD).
• TMS efficacy varies significantly between individuals due to differences in neurophysiology, cortical geometry, and brain connectivity.
• Standard TMS targeting often relies on anatomical landmarks, potentially overlooking crucial network connectivity.

Purpose of the Study:

• To investigate the functional connectivity (FC) of Transcranial Magnetic Stimulation (TMS) targets in the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (OFC).
• To analyze inter-subject variability in TMS-induced electrical field (E-field) patterns and their associated functional brain networks.
• To determine if individual differences in functional brain dynamics or cortical geometry contribute more to downstream network engagement.

Main Methods:

• Generated individualized E-field maps on the cortical surface for 121 subjects using SimNIBS and tetrahedral head models from MRI data.
• Targeted the left dlPFC (F3 position) and left OFC (Fp1 position).
• Analyzed inter-subject variability in E-field patterns, FC, and network membership of TMS targets.

Main Results:

• Identified distinct FC patterns for dlPFC and OFC TMS targets, with significant inter-subject variability.
• Revealed targeting of ventral attention, fronto-parietal, and default-mode networks for dlPFC, and fronto-parietal and default mode networks for OFC.
• Found that while normative data can predict targeted networks, it cannot accurately quantify the relative network loading due to high individual variability in cortical geometry and FC.

Conclusions:

• Characterized the functional connectivity patterns of canonical TMS targets and their variability across individuals.
• High inter-individual variability in cortical geometry and FC likely contributes to the observed variability in TMS physiological and therapeutic outcomes.
• These findings offer insights for refining TMS therapy through a better understanding of its neurophysiological effects and subject-specific targeting.