Defining critical white matter pathways mediating successful subcallosal cingulate deep brain stimulation for treatment-resistant depression

Patricio Riva-Posse, Ki Sueng Choi, Paul E. Holtzheimer, Cameron C. McIntyre, Robert E. Gross, Ashutosh Chaturvedi, Andrea L. Crowell, Steven J. Garlow, Justin K. Rajendra, Helen S. Mayberg

Research output: Contribution to journalArticlepeer-review

336 Scopus citations


Background Subcallosal cingulate white matter (SCC) deep brain stimulation (DBS) is an evolving investigational treatment for depression. Mechanisms of action are hypothesized to involve modulation of activity within a structurally defined network of brain regions involved in mood regulation. Diffusion tensor imaging was used to model white matter connections within this network to identify those critical for successful antidepressant response.

Methods Preoperative high-resolution magnetic resonance imaging data, including diffusion tensor imaging, were acquired in 16 patients with treatment-resistant depression, who then received SCC DBS. Computerized tomography was used postoperatively to locate DBS contacts. The activation volume around the contacts used for chronic stimulation was modeled for each patient retrospectively. Probabilistic tractography was used to delineate the white matter tracts traveling through each activation volume. Patient-specific tract maps were calculated using whole-brain analysis. Clinical evaluations of therapeutic outcome from SCC DBS were defined at 6 months and 2 years.

Results Whole-brain activation volume tractography demonstrated that all DBS responders at 6 months (n = 6) and 2 years (n = 12) shared bilateral pathways from their activation volumes to 1) medial frontal cortex via forceps minor and uncinate fasciculus; 2) rostral and dorsal cingulate cortex via the cingulum bundle; and 3) subcortical nuclei. Nonresponders did not consistently show these connections. Specific anatomical coordinates of the active contacts did not discriminate responders from nonresponders.

Conclusions Patient-specific activation volume tractography modeling may identify critical tracts that mediate SCC DBS antidepressant response. This suggests a novel method for patient-specific target and stimulation parameter selection.

Original languageEnglish
Pages (from-to)963-969
Number of pages7
JournalBiological Psychiatry
Issue number12
StatePublished - 15 Dec 2014
Externally publishedYes


  • Antidepressant response
  • bipolar disorder
  • deep brain stimulation
  • diffusion tensor imaging
  • major depressive disorder
  • subcallosal cingulate
  • subgenual cingulate
  • tractography
  • treatmentresistant depression


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