Article

Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression

Emory University, Atlanta, Georgia, United States
Biological psychiatry (Impact Factor: 10.26). 12/2014; 76(12). DOI: 10.1016/j.biopsych.2014.03.029

ABSTRACT

Background
Deep brain stimulation (DBS) of subcallosal cingulate white matter (SCC) is an evolving investigational treatment for major 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 (DTI) was used to model white matter connections within this network to identify those critical for successful antidepressant response to SCC DBS.

Methods
Pre-operative high-resolution MRI data, including DTI, were acquired in 16 patients with treatment-resistant depression who then received SCC DBS. Computerized tomography was used post-operatively to locate DBS contacts. The activation volume around the active contacts used for chronic stimulation was modeled for each patient retrospectively. Probabilistic tractography was used to delineate the white matter tracts that traveled 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 (AVT) demonstrated that all DBS responders at six 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. Non-responders did not consistently show these connections. Specific anatomical coordinates of the active contacts did not discriminate responders from non-responders.

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

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Available from: Ki Sueng Choi, Sep 27, 2015
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    • "the hypothesis that individually tailored estimation of DBS target might provide better clinical results (Riva-Posse et al., 2014). Despite the promising aspects of the obtained neuroimaging results we fully acknowledge the necessity to evaluate their impact on clinical decision making about the choice of DBS target in MDD, which we will consider in our future research. "
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    • "Although not necessarily an accurate anatomical measure [Thomas et al., 2014], DTIbased tractography nevertheless has been shown to identify certain continuous paths, and changes to those paths, throughout diffusion MR datasets [Jones et al., 2013]. Case studies characterizing optimal DBS targets using DTI have isolated specific relevant white-matter targets [Anthofer et al., 2015; Kovanlikaya et al., 2014; Riva-Posse et al., 2014; Schlaier et al., 2015; Sweet et al., 2014]. However, these studies have been limited to small sample sizes, and tractography measures have been based on deterministic rather than probabilistic tractography, whereas the latter has been demonstrated to provide more robust estimates of underlying white-matter structures [Descoteaux et al., 2009]. "
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