Tractography-activation models applied to subcallosal cingulate deep brain stimulation

Abstract

Deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCWM) is an experimental therapy for major depressive disorder (MDD). The specific axonal pathways that mediate the anti-depressant effects of DBS remain unknown. Patient-specific tractography-activation models (TAMs) are a new tool to help identify pathways modulated by DBS. TAMs consist of four basic components: 1) anatomical and diffusion-weighted imaging data acquired on the patient; 2) probabilistic tractography from the brain region surrounding the implanted DBS electrode; 3) finite element models of the electric field generated by the patient-specific DBS parameter settings; and 4) application of the DBS electric field to multi-compartment cable models of axons, with trajectories defined by the tractography, to predict action potential generation in specific pathways. This study presents TAM predictions from DBS of the SCCWM in one MDD patient. Our findings suggest that small differences in electrode location can generate substantial differences in the directly activated pathways.

Keywords: Accumbens; Axon; Cingulum; Cortex; Depression; White matter.

Copyright © 2013 Elsevier Inc. All rights reserved.

Figures

Figure 1

Tractography-activation models. A) Coronal image of the DBS electrode location. Inset shows the 4 contact lead and the respective contact numbers. Stimulation through contact 3 resulted in the best clinical outcomes. B) Sagittal view of the DBS electrode location. Note that the MRI background image is 3 mm behind the tip of the DBS electrode as not to obscure the tractography results which project in 3D around the electrode in following panels. C) White streamlines represent axon model trajectories passing by the DBS electrode. D) Extracellular voltage distribution imposed upon each axon model from stimulation at contact 3. E,G) Axon models (red streamlines) directly activated by therapeutic stimulation. F,H) Axon models directly activated by non-therapeutic stimulation.