Luke J Norman1, Stephan F Taylor2, Yanni Liu2, Joaquim Radua3, Yann Chye4, Stella J De Wit5, Chaim Huyser6, F Isik Karahanoglu7, Tracy Luks8, Dara Manoach9, Carol Mathews10, Katya Rubia11, Chao Suo4, Odile A van den Heuvel12, Murat Yücel13, Kate Fitzgerald2. 1. Department of Psychiatry, Michigan Medicine, University of Michigan, Ann Arbor, Michigan; Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Electronic address: luken@umich.edu. 2. Department of Psychiatry, Michigan Medicine, University of Michigan, Ann Arbor, Michigan. 3. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Mental Health Research Networking Center, Barcelona, Spain; Centre for Psychiatric Research and Education, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden. 4. Brain and Mental Health Research Hub, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia. 5. Amsterdam Neuroscience, Amsterdam University Medical Centers, Department of Psychiatry, Amsterdam, The Netherlands; Department of Anatomy & Neurosciences, Vrije Universiteit, GGZ inGeest Specialized Mental Health Care, Amsterdam, The Netherlands. 6. Bascule, Academic Centre for Children and Adolescent Psychiatry, Amsterdam, The Netherlands. 7. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 8. Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California. 9. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts. 10. Department of Psychiatry and Center for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, Florida. 11. Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. 12. Amsterdam Neuroscience, Amsterdam University Medical Centers, Department of Psychiatry, Amsterdam, The Netherlands; OCD Team, Haukeland University Hospital, Bergen, Norway. 13. Brain and Mental Health Research Hub, Monash Institute of Cognitive and Clinical Neurosciences, School of Psychological Sciences, Monash University, Melbourne, Australia; Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, Australia.
Abstract
BACKGROUND: Error processing and inhibitory control enable the adjustment of behaviors to meet task demands. Functional magnetic resonance imaging studies report brain activation abnormalities in patients with obsessive-compulsive disorder (OCD) during both processes. However, conclusions are limited by inconsistencies in the literature and small sample sizes. Therefore, the aim here was to perform a meta-analysis of the existing literature using unthresholded statistical maps from previous studies. METHODS: A voxelwise seed-based d mapping meta-analysis was performed using t-maps from studies comparing patients with OCD and healthy control subjects (HCs) during error processing and inhibitory control. For the error processing analysis, 239 patients with OCD (120 male; 79 medicated) and 229 HCs (129 male) were included, while the inhibitory control analysis included 245 patients with OCD (120 male; 91 medicated) and 239 HCs (135 male). RESULTS: Patients with OCD, relative to HCs, showed longer inhibitory control reaction time (standardized mean difference = 0.20, p = .03, 95% confidence interval = 0.016, 0.393) and more inhibitory control errors (standardized mean difference = 0.22, p = .02, 95% confidence interval = 0.039, 0.399). In the brain, patients showed hyperactivation in the bilateral dorsal anterior cingulate cortex, supplementary motor area, and pre-supplementary motor area as well as right anterior insula/frontal operculum and anterior lateral prefrontal cortex during error processing but showed hypoactivation during inhibitory control in the rostral and ventral anterior cingulate cortices and bilateral thalamus/caudate, as well as the right anterior insula/frontal operculum, supramarginal gyrus, and medial orbitofrontal cortex (all seed-based d mapping z value >2, p < .001). CONCLUSIONS: A hyperactive error processing mechanism in conjunction with impairments in implementing inhibitory control may underlie deficits in stopping unwanted compulsive behaviors in the disorder.
BACKGROUND: Error processing and inhibitory control enable the adjustment of behaviors to meet task demands. Functional magnetic resonance imaging studies report brain activation abnormalities in patients with obsessive-compulsive disorder (OCD) during both processes. However, conclusions are limited by inconsistencies in the literature and small sample sizes. Therefore, the aim here was to perform a meta-analysis of the existing literature using unthresholded statistical maps from previous studies. METHODS: A voxelwise seed-based d mapping meta-analysis was performed using t-maps from studies comparing patients with OCD and healthy control subjects (HCs) during error processing and inhibitory control. For the error processing analysis, 239 patients with OCD (120 male; 79 medicated) and 229 HCs (129 male) were included, while the inhibitory control analysis included 245 patients with OCD (120 male; 91 medicated) and 239 HCs (135 male). RESULTS:Patients with OCD, relative to HCs, showed longer inhibitory control reaction time (standardized mean difference = 0.20, p = .03, 95% confidence interval = 0.016, 0.393) and more inhibitory control errors (standardized mean difference = 0.22, p = .02, 95% confidence interval = 0.039, 0.399). In the brain, patients showed hyperactivation in the bilateral dorsal anterior cingulate cortex, supplementary motor area, and pre-supplementary motor area as well as right anterior insula/frontal operculum and anterior lateral prefrontal cortex during error processing but showed hypoactivation during inhibitory control in the rostral and ventral anterior cingulate cortices and bilateral thalamus/caudate, as well as the right anterior insula/frontal operculum, supramarginal gyrus, and medial orbitofrontal cortex (all seed-based d mapping z value >2, p < .001). CONCLUSIONS: A hyperactive error processing mechanism in conjunction with impairments in implementing inhibitory control may underlie deficits in stopping unwanted compulsive behaviors in the disorder.
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