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


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.

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.

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.

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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    ABSTRACT: Background: Deep brain stimulation (DBS) represents an alternative symptomatic treatment for major depressive disorder in case of failure of pharmacotherapy. The sub-genual cingulate-Brodmann area 25 (CG-25), is one of the most widely used targets for electrode implantation. Given the diverging clinical outcome after DBS, there is a pressing need for in-depth study of brain anatomy and function allowing accurate and reliable prognosis before surgery. Methods: We studied five treatment-resistant major depressive disorder patients planned to undergo DBS targeting the CG-25. Before surgery, we acquired high-resolution magnetic resonance (MR) diffusion-weighted images for each patient followed by post-surgery MRI for electrode localization. To estimate individual anatomical connectivity pattern of the active contact location we performed probabilistic diffusion tractography intra-individually. We then correlated connectivity patterns with outcome assessed with standardized clinical tests. Connectivity results were compared between DBS responders and non-responders. Results: We observed in one patient an excellent clinical response after DBS of the bilateral posterior gyrus rectus rather than the initially targeted CG-25. The remaining four patients with DBS of the CG-25 were considered as non-responders. In the case patient, we demonstrate a strong connectivity of the stimulated regions to the medial prefrontal cortex (mPFC), which contrasted to the lower mPFC connectivity in non-responders. Limitations: Confirmation in larger cohorts is needed. Conclusions: We propose the posterior gyrus rectus as viable alternative new target for DBS in major depressive disorder. High connectivity between target and mPFC supports the pivotal role of this region in brain networks involved in mood processing.
    Full-text · Article · Jan 2016 · Journal of Affective Disorders
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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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    ABSTRACT: Deep brain stimulation (DBS) is an effective surgical treatment for movement disorders. Although stimulation sites for movement disorders such as Parkinson's disease are established, the therapeutic mechanisms of DBS remain controversial. Recent research suggests that specific white-matter tract and circuit activation mediates symptom relief. To investigate these questions, we have developed a patient-specific open-source software pipeline called 'DBSproc' for (1) localizing DBS electrodes and contacts from postoperative CT images, (2) processing structural and diffusion MRI data, (3) registering all images to a common space, (4) estimating DBS activation volume from patient-specific voltage and impedance, and (5) understanding the DBS contact-brain connectivity through probabilistic tractography. In this paper, we explain our methodology and provide validation with anatomical and tractographic data. This method can be used to help investigate mechanisms of action of DBS, inform surgical and clinical assessments, and define new therapeutic targets. Hum Brain Mapp, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
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