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Original Article |

Abnormally High Degree Connectivity of the Orbitofrontal Cortex in Obsessive-Compulsive Disorder

Jan C. Beucke, MS; Jorge Sepulcre, MD, PhD; Tanveer Talukdar, MS; Clas Linnman, PhD; Katja Zschenderlein, MS; Tanja Endrass, PhD; Christian Kaufmann, MS; Norbert Kathmann, PhD
JAMA Psychiatry. 2013;70(6):619-629. doi:10.1001/jamapsychiatry.2013.173.
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Importance Neurobiological models of obsessive-compulsive disorder (OCD) predict hyperactivity in brain circuits involving the orbitofrontal cortex and the basal ganglia, but it is unclear whether these areas are also characterized by altered brain network properties.

Objectives To determine regions of abnormal degree connectivity in patients with OCD and to investigate whether connectivity measures are affected by antidepressant medication in OCD.

Design Case-control cross-sectional study using resting-state functional magnetic resonance imaging and a data-driven, model-free method to test for alterations in the degree of whole-brain, distant, and local connectivity in unmedicated patients with OCD compared with healthy controls.

Setting Outpatient clinic for OCD.

Participants Twenty-three patients with OCD (12 women, 11 men) receiving no medication, 23 patients with OCD (14 women, 9 men) treated with antidepressant medication, and 2 equally sized control samples matched for age, sex, handedness, educational level, and IQ.

Main Outcome Measures Statistical parametric maps testing the degree of distant and local functional connectivity of each voxel (hub analysis at voxel level) and OCD symptom severity.

Results Unmedicated patients with OCD showed greater distant connectivity in the orbitofrontal cortex and subthalamic nucleus and greater local connectivity in the orbitofrontal cortex and the putamen. Furthermore, distant connectivity of the orbitofrontal cortex and the putamen positively correlated with global OCD symptom severity. Medicated patients with OCD showed reduced local connectivity of the ventral striatum compared with the unmedicated patients.

Conclusions and Relevance Consistent with neurobiological models of OCD, the orbitofrontal cortex and the basal ganglia are hyperconnected in unmedicated patients. The finding of distant connectivity alterations of the orbitofrontal cortex and the basal ganglia represents initial evidence of greater connections with distant cortical areas outside of corticostriatal circuitry. Furthermore, these data suggest that antidepressant medication may reduce connectivity within corticobasal ganglia-thalamo-cortical circuits in OCD.

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Figure 1. Distant degree connectivity effects. A, Main effects in the orbitofrontal cortex (OFC) displayed for unmedicated patients with obsessive-compulsive disorder (OCD) and matched healthy controls (HCs). B and C, Significantly greater degree of connectivity in the subthalamic nucleus and in the orbitofrontal cortex, respectively, in unmedicated patients compared with HCs. Detailed information regarding signal quality in the OFC is available in eFigure 1 and Author Figure 1. The minimum t value threshold of 3.3 used for display of between-group effects is equivalent to a threshold of P < .001, uncorrected. MNI indicates Montreal Neurological Institute.

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Figure 2. Local degree connectivity effects, considering exclusively a 12-mm sphere around each voxel for computation of degree connectivity. A, Main effects in the orbitofrontal cortex (OFC) displayed for unmedicated patients with obsessive-compulsive disorder (OCD) and matched healthy controls (HCs). B and C, Significantly greater local degree of connectivity in the right dorsal putamen and in the orbitofrontal cortex, respectively, in unmedicated patients compared with HCs. The minimum t value threshold of 3.3 used for display of between-group effects is equivalent to a threshold of P < .001, uncorrected. MNI indicates Montreal Neurological Institute.

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Figure 3. Positive correlation between overall obsessive-compulsive disorder (OCD) symptom severity (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] total scores) and degree connectivity (peak voxels derived from correlational analyses between Y-BOCS scores and distant maps). A, The posterior/lateral orbitofrontal cortex (Montreal Neurological Institute [MNI]XYZ = –34, 20, –16; z = 4.07, r = 0.74, R2 = 0.55, P < .001). B, The left dorsal putamen/pallidum (MNIXYZ = –18, 2, 4; z = 3.65, r = 0.69, R2 = 0.48, P < .001). C, Medial prefrontal cortex/anterior cingulate cortex (MPFC/ACC) (MNIXYZ = –10, 44, 22; z = 3.52, r = 0.67, R2 = 0.45, P < .001) in unmedicated patients. The minimum t value threshold of 3.3 used for display of correlational effects is equivalent to a threshold of P < .001, uncorrected.

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Figure 4. Reduced local connectivity of the ventral striatum in patients with obsessive-compulsive disorder (OCD) treated with antidepressants (Med) (n = 23) in comparison with unmedicated (Unmed) patients with OCD (n = 23). A, Sagittal, coronal, and axial slices displaying the peak of group differences at Montreal Neurological Institute (MNI)XYZ = –14, 14, and –8. B, Simple bar graph shows effects in both OCD groups and healthy controls (HC). Effects are displayed relative to the mean of the respective groups, revealing high similarity between local connectivity of the ventral striatum in medicated patients and HCs. β Values are negative in all 3 groups because the ventral striatum does not represent an extensively locally connected hub in comparison with previously described local hubs, which are, for example, found in motor, somatosensory, and auditory areas.4 The minimum t value threshold of 3.3 used for display of between-group effects is equivalent to a threshold of P < .001, uncorrected.

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