scholarly journals Patient-Specific Connectomic Models Correlate With, But Do Not Predict, Outcomes in Deep Brain Stimulation for Obsessive-Compulsive Disorder

2021 ◽  
Author(s):  
Alik S Widge ◽  
Fan Zhang ◽  
Aishwarya Gosai ◽  
George Papadimitrou ◽  
Peter Wilson-Braun ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Clinical Decision Making ◽  
Diffusion Imaging ◽  
Internal Capsule ◽  
Patient Specific ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Deep Brain

Background: Deep brain stimulation (DBS) of the ventral internal capsule/ventral striatum (VCVS) is an emerging treatment for obsessive-compulsive disorder (OCD). Recently, multiple studies using normative connectomes have correlated DBS outcomes to stimulation of specific white matter tracts. Those studies did not test whether these correlations are clinically predictive, and did not apply cross-validation approaches that are necessary for biomarker development. Further, they did not account for the possibility of systematic differences between DBS patients and the non-diagnosed controls used in normative connectomes. Methods: We performed patient-specific diffusion imaging in 8 patients who underwent VCVS DBS for OCD. We delineated tracts connecting thalamus and subthalamic nucleus (STN) to prefrontal cortex via VCVS. We then calculated which tracts were likely activated by individual patients' DBS settings. We fit multiple statistical models to predict both OCD and depression outcomes from tract activation. We further attempted to predict hypomania, a VCVS DBS complication. We assessed all models' performance on held-out test sets. Results: No model predicted OCD response, depression response, or hypomania above chance. Coefficient inspection partly supported prior reports, in that capture of tracts projecting to cingulate cortex was associated with both YBOCS and MADRS response. In contrast to prior reports, however, tracts connected to STN were not reliably correlated with response. Conclusions: Patient-specific imaging and a guideline-adherent analysis were unable to identify a tractographic target with sufficient effect size to drive clinical decision-making or predict individual outcomes. These findings suggest caution in interpreting the results of normative connectome studies.

scholarly journals Toward a unified connectomic target for deep brain stimulation in obsessive-compulsive disorder

2019 ◽  
Author(s):  
Ningfei Li ◽  
Juan Carlos Baldermann ◽  
Astrid Kibleur ◽  
Svenja Treu ◽  
Harith Akram ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Clinical Improvement ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Internal Capsule ◽  
Anterior Cingulate ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Fiber Tracts ◽  
Deep Brain

AbstractMultiple surgical targets have been proposed for treating obsessive-compulsive disorder (OCD) with deep brain stimulation (DBS). However, different targets may modulate the same neural network responsible for clinical improvement. Here we analyzed data from four cohorts of OCD patients (N = 50) that underwent DBS to the anterior limb of the internal capsule (ALIC), the nucleus accumbens (NAcc) or the subthalamic nucleus (STN). Fiber tracts that were predominantly connected to electrodes in good or poor DBS responders were isolated from a normative structural connectome and assigned a predictive value. Strikingly, the same fiber bundle was related to treatment response when independently analyzing two large training cohorts that targeted either ALIC or STN. This discriminative tract is a subsection of the ALIC and connects frontal regions (such as the dorsal anterior cingulate, dACC, and ventral prefrontal, vlPFC, cortices to the STN). When informing the tract solely based on one cohort (e.g. ALIC), clinical improvements in the other (e.g. STN) could be significantly predicted, and vice versa. Finally, clinical improvements of eight patients from a third center with electrodes in the NAcc and six patients from a fourth center in which electrodes had been implanted in both STN and ALIC were significantly predicted based on this novel tract-based DBS target. Results suggest a functional role of a limbic hyperdirect pathway that projects from dACC and vlPFC to anteriomedial STN. Obsessive-compulsive symptoms seem to be tractable by modulating the specific bundle isolated here. Our results show that connectivity-derived improvement models can inform clinical improvement across DBS targets, surgeons and centers. The identified tract is now three-dimensionally defined in stereotactic standard space and will be made openly available.

Open-label trial of anterior limb of internal capsule–nucleus accumbens deep brain stimulation for obsessive-compulsive disorder: insights gained

2019 ◽  
Vol 90 (7) ◽  
pp. 805-812 ◽  
Author(s):  
Daniel Huys ◽  
Sina Kohl ◽  
Juan Carlos Baldermann ◽  
Lars Timmermann ◽  
Volker Sturm ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Nucleus Accumbens ◽  
Executive Functions ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Internal Capsule ◽  
Obsessive Compulsive ◽  
Open Label ◽  
Compulsive Disorder ◽  
Deep Brain

BackgroundFor more than 15 years, deep brain stimulation (DBS) has served as a last-resort treatment for severe treatment-resistant obsessive-compulsive disorder (OCD).MethodsFrom 2010 to 2016, 20 patients with OCD (10 men/10 women) were included in a single-centre trial with a naturalistic open-label design over 1 year to evaluate the effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region (ALIC-NAcc) on OCD symptoms, executive functions, and personality traits.ResultsALIC-NAcc-DBS significantly decreased OCD symptoms (mean Yale-Brown Obsessive Compulsive Scale reduction 33%, 40% full responders) and improves global functioning without loss of efficacy over 1 year. No significant changes were found in depressive or anxiety symptoms. Our study did not show any effect of ALIC-NAcc-DBS on personality traits or executive functions, and no potential outcome predictors were identified in a post hoc analysis. Other than several individual minor adverse events, ALIC-NAcc-DBS has been shown to be safe, but 35% of patients reported a sudden increase in anxiety and anhedonia after acute cessation of stimulation.ConclusionsWe conclude that ALIC-NAcc-DBS is a well-tolerated and promising last-resort treatment option for OCD. The cause of variability in the outcome remains unclear, and the aspect of reversibility must be examined critically. The present data from one of the largest samples of patients with OCD treated with DBS thus far support the results of previous studies with smaller samples.

scholarly journals The role of diffusion tensor imaging and tractography for deep brain stimulation planning in treatment of obsessive-compulsive disorder

2019 ◽  
Vol 98 (Suppl) ◽  
pp. 13-13
Author(s):  
Mario Minor Murakami Junior ◽  
Fabio Luiz Franceschi Godinho ◽  
Paula Ricci Arantes ◽  
Eberval Gadelha Figueiredo ◽  
Rubens Gisbert Cury ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Diffusion Tensor ◽  
Region Of Interest ◽  
Internal Capsule ◽  
Future Perspective ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Deep Brain

Introduction: Obsessive-compulsive disorder (OCD) is a common, chronic and long-lasting mental disorder. The current first-line therapy for OCD is high doses of selective serotonin reuptake inhibitor (SSRI) and cognitive-behavioral psychotherapy. For patients with refractory symptoms, studies demonstrated that they may respond well to Deep Brain Stimulation (DBS), a technique that can modulate altered neuronal activity. Some stimulation sites are currently being used as targets to DBS and showed good response, but further analyses are necessary to improve the location of the electrodes since some patients demonstrated a poor outcome. Neuroimaging that assess white matter such as diffusion tensor image and tractography can evaluate the quality of the targets and assess the tracts that are affected by the electric field of the electrodes used in the surgery. Our hypothesis is that the patient outcome depends on the trajectory of the tracts that are affected by the electric field.Objectives: Our aim is to investigate which tracts connected with the stimulation sites contribute to clinical improvement effects and weather is possible to predict the outcomes based on connectivity.Methodology: We analyzed 4 patients (2 female) with treatment-refractory obsessive-compulsive disorder undergoing deep brain stimulation targeting the anterior limb of the internal capsule/ nucleus accumbens (ALIC). We will perform tractography analysis of the fibers using the volume of active tissue (VTA) as the region of interest. We will relate the alteration in OCD symptom severity on Yale-Brown obsessive-compulsive scale (Y-BOCS) between the condition before surgery and one-year follow-up with the tracts involved with the stimulation sites using DTI data such as fractal anisotropy and mean diffusivity.Partial Results: Half of the patients did show great improvement and the other two maintained a bad outcome. We found that active stimulation of the ALIC more lateral and posterior of the nucleus was associated with a better outcome. Currently, the description of the tracts involved in patients with better outcomes is performed. The tracts involved with this result will be determined by analysis of DTI and tractography.Discussion and Conclusion: For a future perspective, the results will be important to improve the stimulation sites in DBS surgery resulting in better outcomes.

scholarly journals Deep brain stimulation modulates directional limbic connectivity in obsessive-compulsive disorder

Brain ◽  
2020 ◽  
Vol 143 (5) ◽  
pp. 1603-1612 ◽  
Author(s):  
Egill Axfjord Fridgeirsson ◽  
Martijn Figee ◽  
Judy Luigjes ◽  
Pepijn van den Munckhof ◽  
P Richard Schuurman ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Internal Capsule ◽  
Connectivity Analysis ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
The Impact ◽  
Deep Brain ◽  
Stimulation Of

Abstract Deep brain stimulation is effective for patients with treatment-refractory obsessive-compulsive disorder. Deep brain stimulation of the ventral anterior limb of the internal capsule rapidly improves mood and anxiety with optimal stimulation parameters. To understand these rapid effects, we studied functional interactions within the affective amygdala circuit. We compared resting state functional MRI data during chronic stimulation versus 1 week of stimulation discontinuation in patients, and obtained two resting state scans from matched healthy volunteers to account for test-retest effects. Imaging data were analysed using functional connectivity analysis and dynamic causal modelling. Improvement in mood and anxiety following deep brain stimulation was associated with reduced amygdala-insula functional connectivity. Directional connectivity analysis revealed that deep brain stimulation increased the impact of the ventromedial prefrontal cortex on the amygdala, and decreased the impact of the amygdala on the insula. These results highlight the importance of the amygdala circuit in the pathophysiology of obsessive-compulsive disorder, and suggest a neural systems model through which negative mood and anxiety are modulated by stimulation of the ventral anterior limb of the internal capsule for obsessive-compulsive disorder and possibly other psychiatric disorders.

Deep Brain Stimulation for Obsessive-compulsive Disorder: Using Functional Magnetic Resonance Imaging and Electrophysiological Techniques: Technical Case Report

2007 ◽  
Vol 61 (suppl_5) ◽  
pp. ONSE367-ONSE368 ◽  
Author(s):  
Kenneth B. Baker ◽  
Brian H. Kopell ◽  
Donald Malone ◽  
Craig Horenstein ◽  
Mark Lowe ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Magnetic Resonance ◽  
Obsessive Compulsive Disorder ◽  
Brain Stimulation ◽  
Internal Capsule ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Deep Brain

Abstract Objective And Importance: To demonstrate the pattern of activation associated with electrical stimulation through bilateral deep brain stimulation electrodes placed within the anterior limb of the internal capsule to the level of the ventral striatum for treatment of obsessive-compulsive disorder. Clinical Presentation: A 44-year-old man with a 26-year history of obsessive-compulsive disorder underwent functional magnetic resonance imaging (fMRI) and deep brain stimulation-evoked cortical potential testing after bilateral implantation of deep brain stimulation leads. Stimulation was delivered independently through the distal two contacts of each percutaneously extended lead using an external pulse generator. On postoperative Day 2, we used a 3-Tesla magnetic resonance system to measure changes in the fMRI blood oxygen level-dependent signal using stimulation parameters that were predetermined to demonstrate behavioral effects. Intervention: All studies were well tolerated. Trial stimulations performed intraoperatively as well as on postsurgical Day 1 were associated with acutely elevated mood and reduced anxiety. Although the benefit achieved acutely was relatively symmetric between the bilaterally placed leads, follow-up programming showed a clear advantage to right-sided stimulation. Three of the four fMRI trials demonstrated good activation, with the fourth being moderately corrupted by motion artifact. The beneficial effects observed with right-sided stimulation were associated with activation of the ipsilateral head of the caudate, medial thalamus, and anterior cingulate cortex as well as the contralateral cerebellum. The distribution of the cortical evoked potentials was consistent with the locus of cortical activation observed with fMRI. Conclusion: High-frequency stimulation via a lead placed in the anterior limb of the internal capsule induced widespread hemodynamic changes at both the cortical and subcortical levels including areas typically associated with the pathogenesis of obsessive-compulsive disorder.

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