Brian P Brennan1, Danhong Wang2, Meiling Li3, Chris Perriello4, Jianxun Ren2, Jason A Elias5, Nathaniel P Van Kirk5, Jason W Krompinger5, Harrison G Pope6, Suzanne N Haber7, Scott L Rauch7, Justin T Baker8, Hesheng Liu9. 1. Biological Psychiatry Laboratory, McLean Hospital, Belmont, Massachusetts; Obsessive-Compulsive Disorder Institute, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. Electronic address: brennan@partners.org. 2. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 3. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu. 4. Biological Psychiatry Laboratory, McLean Hospital, Belmont, Massachusetts. 5. Obsessive-Compulsive Disorder Institute, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. 6. Biological Psychiatry Laboratory, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. 7. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. 8. Psychotic Disorders Division, McLean Hospital, Belmont, Massachusetts; Department of Psychiatry, Harvard Medical School, Boston, Massachusetts. 9. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China; Institute for Research and Medical Consultations, Imam Abdulahman Bin Faisal University, Dammam, Saudi Arabia. Electronic address: hesheng@nmr.mgh.harvard.edu.
Abstract
BACKGROUND: Existing functional connectivity studies of obsessive-compulsive disorder (OCD) support a model of circuit dysfunction. However, these group-level observations have failed to yield neuroimaging biomarkers sufficient to serve as a test for the OCD diagnosis, predict current or future symptoms, or predict treatment response, perhaps because these studies failed to account for the substantial intersubject variability in structural and functional brain organization. METHODS: We used functional regions, localized in each of 41 individual OCD patients, to identify cortical connectivity biomarkers of both global and dimension-specific symptom severity and to detect functional connections that track changes in symptom severity following intensive residential treatment. RESULTS: Global OCD symptom severity was directly linked to dysconnectivity between large-scale intrinsic brain networks-particularly among the dorsal attention, default, and frontoparietal networks. Changes within a subset of connections among these networks were associated with symptom resolution. Additionally, distinct and nonoverlapping cortical connectivity biomarkers were identified that were significantly associated with the severity of contamination/washing and responsibility for harm/checking symptoms, highlighting the contribution of dissociable neural networks to specific OCD symptom dimensions. By contrast, when we defined functional regions conventionally, using a population-level brain atlas, we could no longer identify connectivity biomarkers of severity or improvement for any of the symptom dimensions. CONCLUSIONS: Our findings would seem to encourage the use of individual-level approaches to connectivity analyses to better delineate the cortical and subcortical networks underlying symptom severity and improvement at the dimensional level in OCD patients.
BACKGROUND: Existing functional connectivity studies of obsessive-compulsive disorder (OCD) support a model of circuit dysfunction. However, these group-level observations have failed to yield neuroimaging biomarkers sufficient to serve as a test for the OCD diagnosis, predict current or future symptoms, or predict treatment response, perhaps because these studies failed to account for the substantial intersubject variability in structural and functional brain organization. METHODS: We used functional regions, localized in each of 41 individual OCDpatients, to identify cortical connectivity biomarkers of both global and dimension-specific symptom severity and to detect functional connections that track changes in symptom severity following intensive residential treatment. RESULTS: Global OCD symptom severity was directly linked to dysconnectivity between large-scale intrinsic brain networks-particularly among the dorsal attention, default, and frontoparietal networks. Changes within a subset of connections among these networks were associated with symptom resolution. Additionally, distinct and nonoverlapping cortical connectivity biomarkers were identified that were significantly associated with the severity of contamination/washing and responsibility for harm/checking symptoms, highlighting the contribution of dissociable neural networks to specific OCD symptom dimensions. By contrast, when we defined functional regions conventionally, using a population-level brain atlas, we could no longer identify connectivity biomarkers of severity or improvement for any of the symptom dimensions. CONCLUSIONS: Our findings would seem to encourage the use of individual-level approaches to connectivity analyses to better delineate the cortical and subcortical networks underlying symptom severity and improvement at the dimensional level in OCDpatients.
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