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. 2009 Feb 15;65(4):276-82.
doi: 10.1016/j.biopsych.2008.09.021. Epub 2008 Nov 14.

A tractography analysis of two deep brain stimulation white matter targets for depression

David A Gutman  1 , Paul E Holtzheimer, Timothy E J Behrens, Heidi Johansen-Berg, Helen S Mayberg
Affiliations

A tractography analysis of two deep brain stimulation white matter targets for depression

David A Gutman et al. Biol Psychiatry. .

Abstract

Background: Deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCwm) or anterior limb of the internal capsule (ALIC) may be effective in treating depression. Connectivity patterns of these regions may inform on mechanisms of action for DBS of these targets.

Methods: Diffusion tensor imaging (DTI) and probabilistic tractography were performed in 13 nondepressed subjects to determine connectivity patterns of SCCwm and ALIC. Tract maps were generated for each target in each subject, and tract voxels were coded as being unique to either target or shared. Group level tract maps were generated by including only those voxels common to at least 10 of 13 (>75%) subjects.

Results: The two targets have distinct patterns of connectivity with regions of overlap. The SCCwm showed consistent ipsilateral connections to the medial frontal cortex, the full extent of the anterior and posterior cingulate, medial temporal lobe, dorsal medial thalamus, hypothalamus, nucleus accumbens, and the dorsal brainstem. The ALIC seed, in contrast, demonstrated widespread projections to frontal pole, medial temporal lobe, cerebellum, nucleus accumbens, thalamus, hypothalamus, and brainstem. Common to both targets, albeit through distinct white matter bundles, were connections to frontal pole, medial temporal lobe, nucleus accumbens, dorsal thalamus, and hypothalamus.

Conclusions: Connectivity patterns of these two DBS white matter targets suggest distinct neural networks with areas of overlap in regions implicated in depression and antidepressant response.

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Conflict of interest statement

HSM consults to Advanced Neuromodulation Systems (ANS; a division of St. Jude Medical) and has intellectual property rights on deep brain stimulation technology for treating depression that have been licensed to ANS. PEH consults to ANS, Tetragenex, Inc., and AstraZeneca, Inc. DAG, TEJB, and HJ-B have reported no biomedical financial interests or potential conflicts of interest.

Figures

Figure 1
Figure 1
Mean connectivity maps for seeds in the SCCwm (A) (in blue) and ALIC (B) (in red). The ROIs used for the targets are displayed in the first row. Population-based mean tractography maps indicate voxels common to at least 75% of subjects. ALIC, anterior limb of the internal capsule; R, right; ROI, region of interest; SCCwm, subcallosal cingulate white matter.
Figure 2
Figure 2
Unique and common projections for SCCwm and ALIC seeds. Areas of overlap (yellow) are superimposed on the mean tract maps for the SCCwm (blue) and ALIC (red). Areas of overlap indicate voxels shared by projections from both targets for at least 50% of subjects. ACg, anterior cingulate; A-HC, amygdala/hippocampus; ALIC, anterior limb of the internal capsule; DThal, dorsal thalamus; FP, frontal pole; HC, hippocampus; HTh, hypothalamus; mF, medial frontal cortex; NAcc, nucleus accumbens; R, right; SCCwm, subcallosal cingulate white matter.
Figure 3
Figure 3
Seed locations relative to tract maps for each target. Row (A) shows the ALIC tract map (red) with the SCCwm seed superimposed (blue). Row (B) shows the SCCwm tract map (blue) with the ALIC seed superimposed (red). ALIC, anterior limb of the internal capsule; R, right; SCCwm, subcallosal cingulate white matter.
See this image and copyright information in PMC

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