Defining Critical White Matter Pathways Mediating Successful Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression
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.
SourceAvailable from: Arie Kaffman[Show abstract] [Hide abstract]
ABSTRACT: Background: Children exposed to early life stress (ELS) exhibit enlarged amygdala volume in comparison to controls. The primary goal of this study was to examine amygdala volumes in bonnet macaques subjected to maternal variable foraging demand (VFD) rearing, a well-established model of ELS. Preliminary analyses examined the interaction of ELS and the serotonin transporter gene on amygdala volume. Secondary analyses were conducted to examine the association between amygdala volume and other stress-related variables previously found to distinguish VFD and non-VFD reared animals. Methods: Twelve VFD-reared and nine normally reared monkeys completed MRI scans on a 3T system (mean age = 5.2 years). Results: Left amygdala volume was larger in VFD vs. control macaques. Larger amygdala volume was associated with: “high” cerebrospinal fluid concentrations of corticotropin releasing-factor (CRF) determined when the animals were in adolescence (mean age = 2.7 years); reduced fractional anisotropy (FA) of the anterior limb of the internal capsule (ALIC) during young adulthood (mean age = 5.2 years) and timid anxiety-like responses to an intruder during full adulthood (mean age = 8.4 years). Right amygdala volume varied inversely with left hippocampal neurogenesis assessed in late adulthood (mean age = 8.7 years). Exploratory analyses also showed a gene-by-environment effect, with VFD-reared macaques with a single short allele of the serotonin transporter gene exhibiting larger amygdala volume compared to VFD-reared subjects with only the long allele and normally reared controls. Conclusion: These data suggest that the left amygdala exhibits hypertrophy after ELS, particularly in association with the serotonin transporter gene, and that amygdala volume variation occurs in concert with other key stress-related behavioral and neurobiological parameters observed across the lifecycle. Future research is required to understand the mechanisms underlying these diverse and persistent changes associated with ELS and amygdala volume.Frontiers in Behavioral Neuroscience 10/2014; 8:342. DOI:10.3389/fnbeh.2014.00342 · 4.16 Impact Factor
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ABSTRACT: Acute pain induces depressed mood, and chronic pain is known to cause depression. Depression, meanwhile, can also adversely affect pain behaviors ranging from symptomology to treatment response. Pain and depression independently induce long-term plasticity in the central nervous system (CNS). Comorbid conditions, however, have distinct patterns of neural activation. We performed a review of the changes in neural circuitry and molecular signaling pathways that may underlie this complex relationship between pain and depression. We also discussed some of the current and future therapies that are based on this understanding of the CNS plasticity that occurs with pain and depression.Neural Plasticity 01/2015; 2015:504691. DOI:10.1155/2015/504691 · 3.60 Impact Factor
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ABSTRACT: Background Obsessive-compulsive disorder is one of the most disabling of all psychiatric illnesses. Despite available pharmacological and psychotherapeutic treatments about 10% of patients remain severely affected and are considered treatment-refractory. For some of these patients deep brain stimulation offers an appropriate treatment method. The scope of this article is to review the published data and to compare different target structures and their effectiveness.Methods PubMed search, last update June 2013, was conducted using the terms ¿deep brain stimulation¿ and ¿obsessive compulsive disorder¿.ResultsIn total 25 studies were found that reported five deep brain stimulation target structures to treat obsessive-compulsive disorder: the anterior limb of the internal capsule (five studies including 14 patients), nucleus accumbens (eight studies including 37 patients), ventral capsule/ventral striatum (four studies including 29 patients), subthalamic nucleus (five studies including 23 patients) and inferior thalamic peduncle (two studies including 6 patients). Despite the anatomical diversity, deep brain stimulation treatment results in similar response rates for the first four target structures. Inferior thalamic peduncle deep brain stimulation results in higher response rates but these results have to be interpreted with caution due to a very small number of cases. Procedure and device related adverse events are relatively low, as well as stimulation or therapy related side effects. Most stimulation related side effects are transient and decline after stimulation parameters have been changed.Conclusion Deep brain stimulation in treatment-refractory obsessive-compulsive disorder seems to be a relatively safe and promising treatment option. However, based on these studies no superior target structure could be identified. More research is needed to better understand mechanisms of action and response predictors that may help to develop a more personalized approach for these severely affected obsessive compulsive patients.BMC Psychiatry 08/2014; 14(1):214. DOI:10.1186/s12888-014-0214-y · 2.24 Impact Factor