Symptom provocation in obsessive–compulsive disorder: A voxel-based meta-analysis and meta-analytic connectivity modeling

Obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric illness with a complex array of symptoms and potentially distinct neural underpinnings. We employed meta-analysis and connectivity modeling of symptom dimensions to delineate the circuit mechanisms of OCD.With the activation likelihood estimation (ALE) algorithm we performed meta-analysis of whole-brain functional magnetic resonance imaging (fMRI) studies of symptom provocation. We contrasted all OCD patients and controls in a primary analysis and divided the studies according to clinical symptoms in secondary meta-analyses. Finally, we employed meta-analytic connectivity modeling analyses (MACMs) to examine co-activation patterns of the brain regions revealed in the primary meta-analysis.A total of 14 experiments from 12 eligible studies with a total of 238 OCD patients (124 men) and 219 healthy controls (120 men) were included in the primary analysis. OCD patients showed higher activation in the right caudate body/putamen/insula and lower activation in the left orbitofrontal cortex (OFC), left inferior frontal gyrus (IFG), left caudate body/middle cingulate cortex (MCC), right middle temporal gyrus (MTG), middle occipital gyrus (MOG) and right lateral occipital gyrus (LOG). MACMs revealed significant co-activation between left IFG and left caudate body/MCC, left MOG and right LOG, right LOG and MTG. In the secondary meta-analyses, the washing subgroup showed higher activation in the right OFC, bilateral ACC, left MOG and right caudate body.OCD patients showed elevated dorsal striatal activation during symptom provocation. In contrast, the washing subgroup engaged higher activation in frontal, temporal and posterior cortical structures as well as right caudate body. Broadly consistent with the proposition of cortico-striatal-thalamic-cortical circuit dysfunction, these findings highlight potentially distinct neural circuits that may underlie the symptoms and potentially etiological subtypes of OCD.