Ningfei Li1, Barbara Hollunder2, Juan Carlos Baldermann3, Astrid Kibleur4, Svenja Treu5, Harith Akram6, Bassam Al-Fatly7, Bryan A Strange5, Juan A Barcia8, Ludvic Zrinzo6, Eileen M Joyce6, Stephan Chabardes9, Veerle Visser-Vandewalle10, Mircea Polosan9, Jens Kuhn11, Andrea A Kühn2, Andreas Horn12. 1. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Berlin, Germany. Electronic address: ningfei.li@charite.de. 2. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Berlin, Germany; Charité - Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, Berlin, Germany; Berlin School of Mind and Brain, Faculty of Philosophy, Humboldt-Universität zu Berlin, Berlin, Germany. 3. Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne; Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, Cologne, Germany. 4. Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut des Neurosciences (AK, SC, MP), Grenoble; and OpenMind Innovation (AK), Paris, France; OpenMind Innovation, Paris, France. 5. Laboratory for Clinical Neuroscience, Centre for Biomedical Technology, Universidad Politécnica de Madrid, Madrid, Spain. 6. Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom; National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Trust (UCLH), London, United Kingdom. 7. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Berlin, Germany. 8. Neurosurgery Department, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain. 9. Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut des Neurosciences (AK, SC, MP), Grenoble; and OpenMind Innovation (AK), Paris, France. 10. Department of Stereotactic and Functional Neurosurgery, University of Cologne, Cologne, Germany. 11. Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, Cologne, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Johanniter Hospital Oberhausen, Evangelisches Klinikum Niederrhein, Oberhausen, Germany. 12. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Berlin, Germany; Charité - Universitätsmedizin Berlin, Einstein Center for Neurosciences Berlin, Berlin, Germany.
Abstract
BACKGROUND: Multiple deep brain stimulation (DBS) targets have been proposed for treating intractable obsessive-compulsive disorder (OCD). Here, we investigated whether stimulation effects of different target sites would be mediated by one common or several segregated functional brain networks. METHODS: First, seeding from active electrodes of 4 OCD patient cohorts (N = 50) receiving DBS to anterior limb of the internal capsule or subthalamic nucleus zones, optimal functional connectivity profiles for maximal Yale-Brown Obsessive Compulsive Scale improvements were calculated and cross-validated in leave-one-cohort-out and leave-one-patient-out designs. Second, we derived optimal target-specific connectivity patterns to determine brain regions mutually predictive of clinical outcome for both targets and others predictive for either target alone. Functional connectivity was defined using resting-state functional magnetic resonance imaging data acquired in 1000 healthy participants. RESULTS: While optimal functional connectivity profiles showed both commonalities and differences between target sites, robust cross-predictions of clinical improvements across OCD cohorts and targets suggested a shared network. Connectivity to the anterior cingulate cortex, insula, and precuneus, among other regions, was predictive regardless of stimulation target. Regions with maximal connectivity to these commonly predictive areas included the insula, superior frontal gyrus, anterior cingulate cortex, and anterior thalamus, as well as the original stereotactic targets. CONCLUSIONS: Pinpointing the network modulated by DBS for OCD from different target sites identified a set of brain regions to which DBS electrodes associated with optimal outcomes were functionally connected-regardless of target choice. On these grounds, we establish potential brain areas that could prospectively inform additional or alternative neuromodulation targets for obsessive-compulsive disorder.
BACKGROUND: Multiple deep brain stimulation (DBS) targets have been proposed for treating intractable obsessive-compulsive disorder (OCD). Here, we investigated whether stimulation effects of different target sites would be mediated by one common or several segregated functional brain networks. METHODS: First, seeding from active electrodes of 4 OCDpatient cohorts (N = 50) receiving DBS to anterior limb of the internal capsule or subthalamic nucleus zones, optimal functional connectivity profiles for maximal Yale-Brown Obsessive Compulsive Scale improvements were calculated and cross-validated in leave-one-cohort-out and leave-one-patient-out designs. Second, we derived optimal target-specific connectivity patterns to determine brain regions mutually predictive of clinical outcome for both targets and others predictive for either target alone. Functional connectivity was defined using resting-state functional magnetic resonance imaging data acquired in 1000 healthy participants. RESULTS: While optimal functional connectivity profiles showed both commonalities and differences between target sites, robust cross-predictions of clinical improvements across OCD cohorts and targets suggested a shared network. Connectivity to the anterior cingulate cortex, insula, and precuneus, among other regions, was predictive regardless of stimulation target. Regions with maximal connectivity to these commonly predictive areas included the insula, superior frontal gyrus, anterior cingulate cortex, and anterior thalamus, as well as the original stereotactic targets. CONCLUSIONS: Pinpointing the network modulated by DBS for OCD from different target sites identified a set of brain regions to which DBS electrodes associated with optimal outcomes were functionally connected-regardless of target choice. On these grounds, we establish potential brain areas that could prospectively inform additional or alternative neuromodulation targets for obsessive-compulsive disorder.
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