Defining critical white matter pathways mediating successful subcallosal cingulate deep brain stimulation for treatment-resistant depression.
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.
Department of Psychiatry and Behavioral Sciences, Emory University. Electronic address: privapo@emory.edu.
Patricio
P
Riva-Posse
Department of Psychiatry and Behavioral Sciences, Emory University; Wallace H. Coulter Department of Biomedical Engineering, Atlanta, Georgia; Biomedical Imaging Technology Center, Georgia Institute of Technology and Emory University, Atlanta, Georgia.
Ki Sueng
KS
Choi
Department of Psychiatry and Behavioral Sciences, Emory University; Departments of Psychiatry and Surgery, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
Paul E
PE
Holtzheimer
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
Cameron C
CC
McIntyre
Wallace H. Coulter Department of Biomedical Engineering, Atlanta, Georgia; Department of Neurology, Emory University, Atlanta, Georgia; Department of Neurosurgery, Emory University, Atlanta, Georgia.
Robert E
RE
Gross
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
Ashutosh
A
Chaturvedi
Department of Psychiatry and Behavioral Sciences, Emory University.
Andrea L
AL
Crowell
Department of Psychiatry and Behavioral Sciences, Emory University.
Steven J
SJ
Garlow
Department of Psychiatry and Behavioral Sciences, Emory University.
Justin K
JK
Rajendra
Department of Psychiatry and Behavioral Sciences, Emory University; Department of Neurology, Emory University, Atlanta, Georgia.
Helen S
HS
Mayberg
D003337:Corpus Callosum / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods*; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy*; D056324:Diffusion Tensor Imaging; D005260:Female; D006179:Gyrus Cinguli / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008137:Longitudinal Studies; D008297:Male; D066127:White Matter / Q000473:pathology*
Antidepressant response; bipolar disorder; deep brain stimulation; diffusion tensor imaging; major depressive disorder; subcallosal cingulate; subgenual cingulate; tractography; treatment-resistant depression