Symptom Network Modulation by Deep Brain Stimulation in Obsessive-Compulsive Disorder
Poster No:
15
Submission Type:
Abstract Submission
Authors:
Barbara Hollunder1, Garance Meyer2, Ningfei Li1, Clemens Neudorfer2, Nanditha Rajamani1, Cristina Nombela3, Philip Mosley4, Harith Akram5, Nicola Acevedo6, Benjamin Borron7, Tina Chou7, Jurgen Germann8, Juan Pablo Castaño Montoya9, Bryan Strange10, Juan Barcia9, Himanshu Tyagi5, David Castle11, Susan Rossell6, Peter Bosanac12, Carsten Finke1, Andrea Kühn1, Jens Kuhn13, Veerle Visser-Vandewalle13, Stephan Chabardes14, Martijn Figee15, R. Mark Richardson7, G. Rees Cosgrove2, Darin Dougherty7, Shan Siddiqi2, Andres Lozano16, Ludvic Zrinzo5, Eileen Joyce5, Mircea Polosan14, Juan Carlos Baldermann13, Michael Fox2, Andreas Horn2
Institutions:
1Charité - University Medicine Berlin, Berlin, Berlin, 2Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 3Universidad Autónoma de Madrid, Madrid, Madrid, 4University of Queensland, St Lucia, Queensland, 5UCL Queen Square Institute of Neurology, London, London, 6Swinburne University of Technology, Melbourne, VIC, 7Massachusetts General Hospital, Harvard Medical School, Boston, MA, 8Krembil Research Institute, Toronto, Ontario, 9Universidad Complutense de Madrid, Madrid, Madrid, 10Universidad Politécnica de Madrid, Madrid, Madrid, 11University of Tasmania and Centre for Mental Health Service Innovation, Sandy Bay, TAS, 12University of Melbourne, Melbourne, VIC, 13Faculty of Medicine and University Hospital Cologne, Cologne, NRW, 14Université Grenoble Alpes, Grenoble, Rhône-Alpes, 15Icahn School of Medicine at Mount Sinai, New York, NY, 16University Health Network, University of Toronto, Toronto, Ontario, Toronto, Ontario
First Author:
Co-Author(s):
Introduction:
Symptom diversity among patients with obsessive-compulsive disorder (OCD) significantly contributes to outcome variability after deep brain stimulation (DBS) (Figee & Mayberg, 2021). Indeed, the same anatomical site is often targeted, without tailoring the surgical strategy to the symptoms dominating a patient's clinical profile. This approach has proven effective for the "average" OCD patient's cardinal symptomatology by activating a specific fiber bundle in the internal capsule (Baldermann et al., 2021; Li et al., 2020). Nonetheless, encompassing a wider range of dysfunctional circuits may require modulating a combination of symptom tracts (Figee & Mayberg, 2021; Hollunder et al., 2022). Here, we segregate the connectome into a set of therapeutic sub-circuits related to enhancements in obsessions, compulsions, depression, anxiety, cognitive flexibility, and cognitive control.
Methods:
This study relied on retrospective data from a multi-institutional cohort of OCD patients (N=99), all of whom underwent bilateral DBS at one of six stereotactic sites: anterior limb of the internal capsule (ALIC) (N=51), nucleus accumbens (N=15), inferior thalamic peduncle (N=5), bed nucleus of the stria terminalis (N=9), subthalamic nucleus (N=13), or combined stimulation of subthalamic nucleus and ALIC (N=6, four electrodes per patient) (Figure 1). Using a Lead-DBS based preprocessing pipeline (Neudorfer et al., 2023), electrode reconstructions affirmed positioning within the intended target regions for the majority of patients. Combining 3D reconstructions of electrodes and adjacent anatomy, the localized effect of DBS on tracts was estimated via finite element modeling. Symptom improvement was expressed as percent change from preoperative baseline on established rating scales and neuropsychological tests: obsessions vs. compulsions (Yale-Brown Obsessive Compulsive Scale), depression (Beck Depression Inventory / Montgomery Åsperg Depression Rating Scale / Hamilton Depression Inventory), anxiety (Hamilton and Beck Anxiety Inventories / State-Trait Anxiety Inventory, state section), cognitive flexibility (Intra-Extra Dimensional Set Shift Task / Trail Making Test, part B), and cognitive control (Stroop). The generalized DBS Fiber Filtering method (Irmen et al., 2020) was carried out to identify which streamlines of a normative group connectome were discriminative for beneficial effects per symptom domain. Tract models were confirmed using five-fold cross-validation (CV).
·Fig. 1. Overview of electrode placement across obsessive-compulsive disorder (OCD) patients.
Results:
Despite differences in electrode placement across institutions and surgeons (Figure 1), the therapeutic impact on overall obsessive-compulsive symptomatology consistently implicated a common prefronto-cortical pathway traversing the ALIC. This model showed positive in-sample associations (R=.39, p<1e-3) and was robust to five-fold CV (R=.30, p<.01). Plain electrode connections (Figure 2A) could further be segregated into symptom-wise bundles (Figure 2B), with those beneficial for obsessions (in-sample R=.41, p<1e-3) located most dorsally (dorsolateral prefrontal areas), in dorso-ventral direction followed by those for depression (in-sample R=.40, p<1e-3), compulsions (in-sample R=.40, p<1e-3), cognitive control (in-sample R=.54, p<0.01), cognitive flexibility (in-sample R=.49, p=.042), and anxiety (ventromedial prefrontal areas; in-sample R=.66, p<1e-3). Five-fold CVs confirmed generalizability of results for obsession (R=.31, p=.01), compulsion (R=.26, p=.037), and anxiety models (R=.63, p<1e-3), but not significantly for depression (R=.15, p=.227), cognitive control (R=.22, p=.315), and cognitive flexibility (R=.10, p=.679).
·Fig. 2. Multi-symptom taxonomy of therapeutic tracts for deep brain stimulation (DBS) in obsessive-compulsive disorder (OCD).
Conclusions:
Fundamentally, our results may enhance our comprehension of the pathophysiological underpinnings and operative mechanisms of DBS relevant to various OCD symptoms. These insights could be instrumental for addressing symptoms transcending different diagnoses, or for customizing treatments to unique symptom clusters exhibited by individual patients.
Brain Stimulation:
Deep Brain Stimulation 1
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity
Keywords:
Anxiety
Basal Ganglia
Cognition
Obessive Compulsive Disorder
Psychiatric Disorders
STRUCTURAL MRI
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
Other - Deep Brain Stimulation; Depression; Compulsivity
1|2Indicates the priority used for review
Provide references using author date format
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