Comparison of structural connectomes for modeling deep brain stimulation pathway activation.

Introduction: Structural connectivity models of the brain are commonly employed to identify pathways that are directly activated during deep brain stimulation (DBS). However, various connectomes differ in the technical parameters, parcellation schemes, and methodological approaches used in their construction.

Objective: The goal of this study was to compare and quantify variability in DBS pathway activation predictions when using different structural connectomes, while using identical electrode placements and stimulation volumes in the brain.

Approach: We analyzed four example structural connectomes: 1) Horn normative connectome (whole brain), 2) Yeh population-averaged tract-to-region pathway atlas (whole brain), 3) Petersen histology-based pathway atlas (subthalamic focused), and 4) Majtanik histology-based pathway atlas (anterior thalamus focused). DBS simulations were performed with each connectome, at four generalized locations for DBS electrode placement: 1) subthalamic nucleus, 2) anterior nucleus of thalamus, 3) ventral capsule, and 4) ventral intermediate nucleus of thalamus.

Results: The choice of connectome used in the simulations resulted in notably distinct pathway activation predictions, and quantitative analysis indicated little congruence in the predicted patterns of brain network connectivity. The Horn and Yeh tractography-based connectomes provided estimates of DBS connectivity for any stimulation location in the brain, but have limitations in their anatomical validity. The Petersen and Majtanik histology-based connectomes are more anatomically realistic, but are only applicable to specific DBS targets because of their limited representation of pathways.

Significance: The widely varying and inconsistent inferences of DBS network connectivity raises substantial concern regarding the general reliability of connectomic DBS studies, especially those that lack anatomical and/or electrophysiological validation in their analyses.